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P Ro, supplied by Proteintech, used in various techniques. Bioz Stars score: 93/100, based on 20 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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Fgl2 deficiency enhances intestinal mucosal immunity against infection. Intestinal trichinella infection stage: Larvae were harvested from the muscles of mice infected with Trichinella for more than 45 days and were administered via gavage to WT ( T. s ) and KO ( T. s ) mice at a density of 200–400 larvae per 10–200 µL volume. After 5–7 days of infection, mice were euthanized, and spleen, mLN, PPs, and duodenum were collected. (a–h) Flow cytometric analysis of B cell subsets including follicular (FO), transitional 1 (T1), transitional 2 (T2), germinal center (GC) B cells, plasmablasts (PBC), plasma cells (PC), IgA + B cells, and IgA + plasma cells—in the spleen, mesenteric lymph nodes (mLN), and Peyer's patches (PPs) from Trichinella spiralis ‐infected WT and KO mice. Representative dot plots and the mean percentages of each subset in the spleen are shown ( n = 5 per group). (i) Immunofluorescence analysis of IgA and CD138 deposition in duodenum tissue sections (green staining for IgA, purple staining for CD138). Shown are representative duodenum and lung sections using a ×60 objective. Scale bar, 10 µm. (j) Hematoxylin and eosin (HE) staining of duodenum sections from WT and KO infected mice. Take the duodenum of the mice that have been infected for 7 days. Shown are representative duodenum using a ×60 objective. Scale bar, 25 µm. Error bars represent the mean (±SD). * p < 0.05, ** p < 0.01, **** p < 0.0001, ns: no significant difference.

Journal: MedComm

Article Title: Fibrinogen‐Like Protein 2 Modulates B Cell Mucosal Immunity by Suppressing Receptor for Activated C‐Kinase 1‐Mediated AKT Phosphorylation

doi: 10.1002/mco2.70633

Figure Lengend Snippet: Fgl2 deficiency enhances intestinal mucosal immunity against infection. Intestinal trichinella infection stage: Larvae were harvested from the muscles of mice infected with Trichinella for more than 45 days and were administered via gavage to WT ( T. s ) and KO ( T. s ) mice at a density of 200–400 larvae per 10–200 µL volume. After 5–7 days of infection, mice were euthanized, and spleen, mLN, PPs, and duodenum were collected. (a–h) Flow cytometric analysis of B cell subsets including follicular (FO), transitional 1 (T1), transitional 2 (T2), germinal center (GC) B cells, plasmablasts (PBC), plasma cells (PC), IgA + B cells, and IgA + plasma cells—in the spleen, mesenteric lymph nodes (mLN), and Peyer's patches (PPs) from Trichinella spiralis ‐infected WT and KO mice. Representative dot plots and the mean percentages of each subset in the spleen are shown ( n = 5 per group). (i) Immunofluorescence analysis of IgA and CD138 deposition in duodenum tissue sections (green staining for IgA, purple staining for CD138). Shown are representative duodenum and lung sections using a ×60 objective. Scale bar, 10 µm. (j) Hematoxylin and eosin (HE) staining of duodenum sections from WT and KO infected mice. Take the duodenum of the mice that have been infected for 7 days. Shown are representative duodenum using a ×60 objective. Scale bar, 25 µm. Error bars represent the mean (±SD). * p < 0.05, ** p < 0.01, **** p < 0.0001, ns: no significant difference.

Article Snippet: Fgl2‐ KO mice (C57BL/6J background, male) were generated by Shanghai Model Organisms Center, Inc. (Shanghai, China).

Techniques: Infection, Muscles, Clinical Proteomics, Immunofluorescence, Staining

Fgl2 deficiency leads to abnormal splenic immune profiling and B cell immunoglobulin heavy constant alpha 1 (IGHA) clonal heterogeneity. (a) Uniform manifold approximation and projection (UMAP) plots of Single‐cell sequencing of WT and KO splenic B cell subsets. Each dot represents a single cell. (b) UMAP plot highlighting the cellular composition, showing an expansion of specific subsets in KO mice (blue), primarily B cell_sp1, B cell_sp2, B cell_sp3, B cell_sp4, and plasma cells, compared with WT mice. (c) Bar plot showing differences in cell subsets between KO and WT mice. (d) UMAP displaying B cell_sp1, B cell_sp2, B cell_sp3, and B cell_sp4 as B cells with genes in the cell‐constant region, the v gene of the predominant clones, the genes in a predominant B cell clone, and the counts of the predominant B cell clone subsets (scBCR‐seq data). (e) UMAP feature plots showing the expression of selected marker genes ( Gzma , Gzmb , Ccl5 ) across cell subsets, with expression enriched in the B cell_sp1‐4 clusters. (f) Immunofluorescence analysis was conducted on the deposition of Gzma, Gzmb, and Ccl5 in the spleen tissues of WT and KO mice. Shown are representative spleen sections using a ×60 objective. Scale bar, 10 µm. (g) Using Image‐Pro Plus 6.0 (Media Cybernetics, Inc., Rockville, MD, USA), each photo was analyzed to obtain the cumulative optical density value (IOD) of each photo as well as the pixel area of the tissue (AREA). The average optical density value (mean density) was also calculated (WT n = 3, KO n = 3). (h) Gene set enrichment analysis (GSEA) analysis of B cell_sp1, B cell_sp2, B cell_sp3, and B cell_sp4 subsets, compared with WT B cells.

Journal: MedComm

Article Title: Fibrinogen‐Like Protein 2 Modulates B Cell Mucosal Immunity by Suppressing Receptor for Activated C‐Kinase 1‐Mediated AKT Phosphorylation

doi: 10.1002/mco2.70633

Figure Lengend Snippet: Fgl2 deficiency leads to abnormal splenic immune profiling and B cell immunoglobulin heavy constant alpha 1 (IGHA) clonal heterogeneity. (a) Uniform manifold approximation and projection (UMAP) plots of Single‐cell sequencing of WT and KO splenic B cell subsets. Each dot represents a single cell. (b) UMAP plot highlighting the cellular composition, showing an expansion of specific subsets in KO mice (blue), primarily B cell_sp1, B cell_sp2, B cell_sp3, B cell_sp4, and plasma cells, compared with WT mice. (c) Bar plot showing differences in cell subsets between KO and WT mice. (d) UMAP displaying B cell_sp1, B cell_sp2, B cell_sp3, and B cell_sp4 as B cells with genes in the cell‐constant region, the v gene of the predominant clones, the genes in a predominant B cell clone, and the counts of the predominant B cell clone subsets (scBCR‐seq data). (e) UMAP feature plots showing the expression of selected marker genes ( Gzma , Gzmb , Ccl5 ) across cell subsets, with expression enriched in the B cell_sp1‐4 clusters. (f) Immunofluorescence analysis was conducted on the deposition of Gzma, Gzmb, and Ccl5 in the spleen tissues of WT and KO mice. Shown are representative spleen sections using a ×60 objective. Scale bar, 10 µm. (g) Using Image‐Pro Plus 6.0 (Media Cybernetics, Inc., Rockville, MD, USA), each photo was analyzed to obtain the cumulative optical density value (IOD) of each photo as well as the pixel area of the tissue (AREA). The average optical density value (mean density) was also calculated (WT n = 3, KO n = 3). (h) Gene set enrichment analysis (GSEA) analysis of B cell_sp1, B cell_sp2, B cell_sp3, and B cell_sp4 subsets, compared with WT B cells.

Article Snippet: Fgl2‐ KO mice (C57BL/6J background, male) were generated by Shanghai Model Organisms Center, Inc. (Shanghai, China).

Techniques: Single Cell, Sequencing, Clinical Proteomics, Clone Assay, Expressing, Marker, Immunofluorescence

Fgl2 deficiency regulates B cell differentiation and adhesion. (a–h) Flow cytometric analysis of splenic FO, T1, T2, and GC B cell subsets in uninfected (steady‐state), 8‐week‐old WT and Fgl2 KO mice ( n = 5 per group). Representative plots, along with summary graphs of percentages and absolute numbers, are shown. (i) Pseudotime trajectory analysis revealed 3 branches of splenic B cells, and most B cells in the KO group located on a unique branch, separated from the WT group, at a unique state, and with larger pseudotime values than the WT group. Plasma cells and all specific B cells cluster (B_sp1‐4) were located almost exclusively on the KO unique branch, and the less mature B cells, such as follicular B cells, marginal zone B cells, naïve B cells, transitional B cells, and B cells with somatic hypermutation, were located on the WT branches. The heatmap of the DEGs between KO branch and WT branches showed the difference in gene expression patterns. (j) CTV‐ and CFSE‐labeled WT and KO splenic B cells were mixed in a 1:1 ratio and injected into WT recipient mice. After 3 h, blood, bone marrow (BM), spleen, and peripheral lymph nodes (pLN) cells of recipient mice were stained with anti‐B220‐APC, and the proportions of WT and KO cells were compared. (k) Statistical analysis of adhesion molecules and integrin expression on blood B cells from WT and KO mice, along with representative flow cytometry plots and histograms for β1 integrin ( n = 5). Data are shown as mean ± SD. Each symbol represents a single mouse. * p < 0.05, ** p < 0.01, ns: not significant.

Journal: MedComm

Article Title: Fibrinogen‐Like Protein 2 Modulates B Cell Mucosal Immunity by Suppressing Receptor for Activated C‐Kinase 1‐Mediated AKT Phosphorylation

doi: 10.1002/mco2.70633

Figure Lengend Snippet: Fgl2 deficiency regulates B cell differentiation and adhesion. (a–h) Flow cytometric analysis of splenic FO, T1, T2, and GC B cell subsets in uninfected (steady‐state), 8‐week‐old WT and Fgl2 KO mice ( n = 5 per group). Representative plots, along with summary graphs of percentages and absolute numbers, are shown. (i) Pseudotime trajectory analysis revealed 3 branches of splenic B cells, and most B cells in the KO group located on a unique branch, separated from the WT group, at a unique state, and with larger pseudotime values than the WT group. Plasma cells and all specific B cells cluster (B_sp1‐4) were located almost exclusively on the KO unique branch, and the less mature B cells, such as follicular B cells, marginal zone B cells, naïve B cells, transitional B cells, and B cells with somatic hypermutation, were located on the WT branches. The heatmap of the DEGs between KO branch and WT branches showed the difference in gene expression patterns. (j) CTV‐ and CFSE‐labeled WT and KO splenic B cells were mixed in a 1:1 ratio and injected into WT recipient mice. After 3 h, blood, bone marrow (BM), spleen, and peripheral lymph nodes (pLN) cells of recipient mice were stained with anti‐B220‐APC, and the proportions of WT and KO cells were compared. (k) Statistical analysis of adhesion molecules and integrin expression on blood B cells from WT and KO mice, along with representative flow cytometry plots and histograms for β1 integrin ( n = 5). Data are shown as mean ± SD. Each symbol represents a single mouse. * p < 0.05, ** p < 0.01, ns: not significant.

Article Snippet: Fgl2‐ KO mice (C57BL/6J background, male) were generated by Shanghai Model Organisms Center, Inc. (Shanghai, China).

Techniques: Cell Differentiation, Clinical Proteomics, Gene Expression, Labeling, Injection, Staining, Expressing, Flow Cytometry

Fgl2 negatively regulates BCR signal transduction and actin polymerization. (a) WT and KO splenic B cells were isolated and cultured for 24 h with F(ab') 2 anti‐mouse Ig (M + G) and CD40, followed by proteomic and Gene Ontology (GO) analysis. (b) The cells were incubated with biotin‐conjugated F(ab') 2 anti‐mouse Ig (M + G) and streptavidin, followed by activation at 37°C for 5, 10, and 30 min. Western blot analysis was performed to detect the expression levels of pY, pSYK, pBTK, pSHIP‐1, pWASP, and DOCK8. (c–j) Splenic B cells from WT and KO mice were stimulated with AF594 F(ab') 2 goat anti‐mouse IgG + IgM (10 µg/mL), then fixed, permeabilized, and stained for Fgl2, pSHIP‐1, pSYK, pY, or pBTK. The colocalization of Fgl2, pSHIP‐1, pSYK, pY, or pBTK with the BCR was analyzed using Pearson's correlation coefficient. Images were captured using a Zeiss confocal fluorescence microscope and analyzed using the NIS‐elements AR 5.01. Scale bars, 2.5 µm. (k) Ca 2+ flux in splenic B cells from WT and KO mice stimulated with 10 µg/mL biotin‐conjugated F(ab') 2 anti‐mouse Ig (M + G). Data are representative of three independent experiments. (l) Splenic B cells from WT and KO mice were incubated with AF546‐mB‐Fab‐anti‐Ig tethered to lipid bilayers for 3, 5, and 7 min, then fixed, permeabilized, and stained for pWASP/F‐actin. Shown are representative images captured using Nikon TIRFm from three independent experiments. Scale bars, 2.5 µm. (m, n) The MFI of pWASP, F‐actin in the contact zone were quantified using NIS‐Elements AR 5.0.1 software. Data are shown as mean ± SD. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.

Journal: MedComm

Article Title: Fibrinogen‐Like Protein 2 Modulates B Cell Mucosal Immunity by Suppressing Receptor for Activated C‐Kinase 1‐Mediated AKT Phosphorylation

doi: 10.1002/mco2.70633

Figure Lengend Snippet: Fgl2 negatively regulates BCR signal transduction and actin polymerization. (a) WT and KO splenic B cells were isolated and cultured for 24 h with F(ab') 2 anti‐mouse Ig (M + G) and CD40, followed by proteomic and Gene Ontology (GO) analysis. (b) The cells were incubated with biotin‐conjugated F(ab') 2 anti‐mouse Ig (M + G) and streptavidin, followed by activation at 37°C for 5, 10, and 30 min. Western blot analysis was performed to detect the expression levels of pY, pSYK, pBTK, pSHIP‐1, pWASP, and DOCK8. (c–j) Splenic B cells from WT and KO mice were stimulated with AF594 F(ab') 2 goat anti‐mouse IgG + IgM (10 µg/mL), then fixed, permeabilized, and stained for Fgl2, pSHIP‐1, pSYK, pY, or pBTK. The colocalization of Fgl2, pSHIP‐1, pSYK, pY, or pBTK with the BCR was analyzed using Pearson's correlation coefficient. Images were captured using a Zeiss confocal fluorescence microscope and analyzed using the NIS‐elements AR 5.01. Scale bars, 2.5 µm. (k) Ca 2+ flux in splenic B cells from WT and KO mice stimulated with 10 µg/mL biotin‐conjugated F(ab') 2 anti‐mouse Ig (M + G). Data are representative of three independent experiments. (l) Splenic B cells from WT and KO mice were incubated with AF546‐mB‐Fab‐anti‐Ig tethered to lipid bilayers for 3, 5, and 7 min, then fixed, permeabilized, and stained for pWASP/F‐actin. Shown are representative images captured using Nikon TIRFm from three independent experiments. Scale bars, 2.5 µm. (m, n) The MFI of pWASP, F‐actin in the contact zone were quantified using NIS‐Elements AR 5.0.1 software. Data are shown as mean ± SD. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.

Article Snippet: Fgl2‐ KO mice (C57BL/6J background, male) were generated by Shanghai Model Organisms Center, Inc. (Shanghai, China).

Techniques: Transduction, Isolation, Cell Culture, Incubation, Activation Assay, Western Blot, Expressing, Staining, Fluorescence, Microscopy, Software

Fgl2‐Rack1 interaction regulates B cell signaling. (a) The Rack1 gene was constructed into the pGADT7 vector. Using the Y2H system (Takara, Kyoto, Japan), plasmid pGADT7‐Rack1 and pGBKT7 were transferred into yeast strain Y2H Gold and coated on DDO, TDO, and QDO plates for 3–5 days at 30°C. The vector of pGADT7‐Rack1 without self‐activation and toxicity and pGBKT7‐Fgl2‐JD were transferred into the Y2H Gold strain and coated in DDO and QDO plates for 3–5 days at 30°C. The growth of monoclonal colonies on the selection plates confirmed a direct interaction between the two proteins. (b) Co‐immunoprecipitation (CO‐IP) assay was performed using lysates from WT mouse splenic B cells. Anti‐Rack1 antibody (control: rabbit IgG) or anti‐Fgl2 antibody was used for immunoprecipitation. The interaction between endogenous Rack1 and endogenous Fgl2 was detected by western blot. (c) GST pull‐down assay showing the direct interaction between Rack1 and Fgl2. GST alone or GST‐Rack1 fusion protein was incubated with His‐Fgl2 protein, and the interaction was detected by western blot. (d, e) Computational modeling of the Fgl2 and Rack1 interaction. Three‐dimensional structural models of the Fgl2 and Rack1 proteins were generated using AlphaFold3. To investigate the potential interaction between Fgl2 and Rack1, we performed molecular docking simulations, also using AlphaFold3. The optimal predicted structures for both proteins were used as input. The simulation calculated potential binding interfaces by evaluating factors such as surface electrostatic potential, hydrogen bonding possibilities, and hydrophobic interactions to predict the most likely binding mode between Fgl2 and Rack1. (f, g) Splenic B cells from WT and KO mice were stimulated with AF594‐conjugated F(ab′) 2 goat anti‐mouse IgG + IgM (10 µg/mL) for 0 and 5 min, then fixed, permeabilized, and stained for Fgl2 and Rack1. Co‐localization between Fgl2 and Rack1 was quantified using the Pearson correlation coefficient. Shown are representative blots from three independent experiments. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.

Journal: MedComm

Article Title: Fibrinogen‐Like Protein 2 Modulates B Cell Mucosal Immunity by Suppressing Receptor for Activated C‐Kinase 1‐Mediated AKT Phosphorylation

doi: 10.1002/mco2.70633

Figure Lengend Snippet: Fgl2‐Rack1 interaction regulates B cell signaling. (a) The Rack1 gene was constructed into the pGADT7 vector. Using the Y2H system (Takara, Kyoto, Japan), plasmid pGADT7‐Rack1 and pGBKT7 were transferred into yeast strain Y2H Gold and coated on DDO, TDO, and QDO plates for 3–5 days at 30°C. The vector of pGADT7‐Rack1 without self‐activation and toxicity and pGBKT7‐Fgl2‐JD were transferred into the Y2H Gold strain and coated in DDO and QDO plates for 3–5 days at 30°C. The growth of monoclonal colonies on the selection plates confirmed a direct interaction between the two proteins. (b) Co‐immunoprecipitation (CO‐IP) assay was performed using lysates from WT mouse splenic B cells. Anti‐Rack1 antibody (control: rabbit IgG) or anti‐Fgl2 antibody was used for immunoprecipitation. The interaction between endogenous Rack1 and endogenous Fgl2 was detected by western blot. (c) GST pull‐down assay showing the direct interaction between Rack1 and Fgl2. GST alone or GST‐Rack1 fusion protein was incubated with His‐Fgl2 protein, and the interaction was detected by western blot. (d, e) Computational modeling of the Fgl2 and Rack1 interaction. Three‐dimensional structural models of the Fgl2 and Rack1 proteins were generated using AlphaFold3. To investigate the potential interaction between Fgl2 and Rack1, we performed molecular docking simulations, also using AlphaFold3. The optimal predicted structures for both proteins were used as input. The simulation calculated potential binding interfaces by evaluating factors such as surface electrostatic potential, hydrogen bonding possibilities, and hydrophobic interactions to predict the most likely binding mode between Fgl2 and Rack1. (f, g) Splenic B cells from WT and KO mice were stimulated with AF594‐conjugated F(ab′) 2 goat anti‐mouse IgG + IgM (10 µg/mL) for 0 and 5 min, then fixed, permeabilized, and stained for Fgl2 and Rack1. Co‐localization between Fgl2 and Rack1 was quantified using the Pearson correlation coefficient. Shown are representative blots from three independent experiments. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.

Article Snippet: Fgl2‐ KO mice (C57BL/6J background, male) were generated by Shanghai Model Organisms Center, Inc. (Shanghai, China).

Techniques: Construct, Plasmid Preparation, Activation Assay, Selection, Co-Immunoprecipitation Assay, Control, Immunoprecipitation, Western Blot, Pull Down Assay, Incubation, Generated, Binding Assay, Staining

Fgl2 regulates B cell metabolism and differentiation by inhibiting Rack1‐mediated AKT activation. (a) WT and KO splenic B cells were isolated and cultured for 24 h in the presence of F(ab') 2 anti‐mouse Ig (M + G) and CD40, followed by comparison of their metabolic products and metabolomic analysis (WT n = 5, KO n = 6). (b) Oxygen consumption rate (OCR) measurement in WT and KO B cells to assess mitochondrial respiration. (c) Extracellular acidification rate (ECAR) measurement in WT and KO B cells to evaluate glycolytic activity. (d) Transmission electron microscopy (TEM) analysis of subcellular structures, including mitochondria, in WT and KO B cells after 24 h of culture in the presence of F(ab') 2 anti‐mouse Ig (M + G) and CD40. (e) Western blot analysis of phosphorylated proteins (pPI3K, pMTOR, pAKT, pFOXO1, pS6) in splenic B cells activated with biotin‐conjugated F(ab') 2 anti‐mouse Ig(M+G) and streptavidin. (f) The spleen B cells of KO mice were pretreated with 20 µM Rack1 inhibitor (Harringtonolide) and 10 ng Fgl2 protein for 2 h, and then stimulated with sAg(F(ab') 2 anti‐mouse Ig(M+G)) for 5 min together with the B cells of WT mice. Subsequently, the levels of Rack1, pAKT, pSYK, and pBTK were detected by western blotting. (g, h) At 8 weeks of age, WT and KO mice were intraperitoneally injected with 0.5 µg/g of physiological saline or Rack1 inhibitor twice a week for 28 days, and then MZ, GC B cells, and IgA+ plasma cells were analyzed by flow cytometry (WT n = 5, KO n = 5). (i) At 8 weeks of age, WT and KO mice were intraperitoneally injected with 0.5 µg/g of physiological saline or Rack1 inhibitor twice a week for 28 days. Splenic B cells were collected and stimulated with sAg (F(ab') 2 anti‐mouse Ig(M+G)). Western blotting was used to detect the levels of Rack1 and pAKT. Data are presented as mean ± SD. * p < 0.05, ** p < 0.01, **** p < 0.0001, ns: not significant.

Journal: MedComm

Article Title: Fibrinogen‐Like Protein 2 Modulates B Cell Mucosal Immunity by Suppressing Receptor for Activated C‐Kinase 1‐Mediated AKT Phosphorylation

doi: 10.1002/mco2.70633

Figure Lengend Snippet: Fgl2 regulates B cell metabolism and differentiation by inhibiting Rack1‐mediated AKT activation. (a) WT and KO splenic B cells were isolated and cultured for 24 h in the presence of F(ab') 2 anti‐mouse Ig (M + G) and CD40, followed by comparison of their metabolic products and metabolomic analysis (WT n = 5, KO n = 6). (b) Oxygen consumption rate (OCR) measurement in WT and KO B cells to assess mitochondrial respiration. (c) Extracellular acidification rate (ECAR) measurement in WT and KO B cells to evaluate glycolytic activity. (d) Transmission electron microscopy (TEM) analysis of subcellular structures, including mitochondria, in WT and KO B cells after 24 h of culture in the presence of F(ab') 2 anti‐mouse Ig (M + G) and CD40. (e) Western blot analysis of phosphorylated proteins (pPI3K, pMTOR, pAKT, pFOXO1, pS6) in splenic B cells activated with biotin‐conjugated F(ab') 2 anti‐mouse Ig(M+G) and streptavidin. (f) The spleen B cells of KO mice were pretreated with 20 µM Rack1 inhibitor (Harringtonolide) and 10 ng Fgl2 protein for 2 h, and then stimulated with sAg(F(ab') 2 anti‐mouse Ig(M+G)) for 5 min together with the B cells of WT mice. Subsequently, the levels of Rack1, pAKT, pSYK, and pBTK were detected by western blotting. (g, h) At 8 weeks of age, WT and KO mice were intraperitoneally injected with 0.5 µg/g of physiological saline or Rack1 inhibitor twice a week for 28 days, and then MZ, GC B cells, and IgA+ plasma cells were analyzed by flow cytometry (WT n = 5, KO n = 5). (i) At 8 weeks of age, WT and KO mice were intraperitoneally injected with 0.5 µg/g of physiological saline or Rack1 inhibitor twice a week for 28 days. Splenic B cells were collected and stimulated with sAg (F(ab') 2 anti‐mouse Ig(M+G)). Western blotting was used to detect the levels of Rack1 and pAKT. Data are presented as mean ± SD. * p < 0.05, ** p < 0.01, **** p < 0.0001, ns: not significant.

Article Snippet: Fgl2‐ KO mice (C57BL/6J background, male) were generated by Shanghai Model Organisms Center, Inc. (Shanghai, China).

Techniques: Activation Assay, Isolation, Cell Culture, Comparison, Metabolomic, Activity Assay, Transmission Assay, Electron Microscopy, Western Blot, Injection, Saline, Clinical Proteomics, Flow Cytometry

Fgl2 regulates B cells in patients with mucosal immune conditions by inhibiting Rack1‐mediated AKT activation. (a) Flow cytometric analysis of the proportion of B cells in peripheral blood from healthy controls (HC, n = 9) and COVID‐19 patients (patient, n = 8). (b–d) Flow cytometric histograms and mean fluorescence intensity (MFI) of IgA, Fgl2, and Rack1 expression on B cells in healthy controls and COVID‐19 patients. (e, f) Flow cytometric analysis of B cell subsets in PBMCs from HCs and patients. Representative flow cytometric plots of memory B cells, Naïve B cells, transitional B cells, and plasma B cells in the peripheral blood of healthy controls and COVID‐19 patients. (g, h) The patient's PBMCs were first pretreated with 20 µM Rack1 inhibitor (Harringtonolide) for 2 h, and then stimulated with human sAg for 5 min. Phosphorylation flow cytometry was used to detect the expression levels of Rack1, pAKT, pBTK, and pSYK in B cells (patient, n = 6). Data are presented as mean ± SD. * p < 0.05, ** p < 0.01, **** p < 0.0001, ns: not significant.

Journal: MedComm

Article Title: Fibrinogen‐Like Protein 2 Modulates B Cell Mucosal Immunity by Suppressing Receptor for Activated C‐Kinase 1‐Mediated AKT Phosphorylation

doi: 10.1002/mco2.70633

Figure Lengend Snippet: Fgl2 regulates B cells in patients with mucosal immune conditions by inhibiting Rack1‐mediated AKT activation. (a) Flow cytometric analysis of the proportion of B cells in peripheral blood from healthy controls (HC, n = 9) and COVID‐19 patients (patient, n = 8). (b–d) Flow cytometric histograms and mean fluorescence intensity (MFI) of IgA, Fgl2, and Rack1 expression on B cells in healthy controls and COVID‐19 patients. (e, f) Flow cytometric analysis of B cell subsets in PBMCs from HCs and patients. Representative flow cytometric plots of memory B cells, Naïve B cells, transitional B cells, and plasma B cells in the peripheral blood of healthy controls and COVID‐19 patients. (g, h) The patient's PBMCs were first pretreated with 20 µM Rack1 inhibitor (Harringtonolide) for 2 h, and then stimulated with human sAg for 5 min. Phosphorylation flow cytometry was used to detect the expression levels of Rack1, pAKT, pBTK, and pSYK in B cells (patient, n = 6). Data are presented as mean ± SD. * p < 0.05, ** p < 0.01, **** p < 0.0001, ns: not significant.

Article Snippet: Fgl2‐ KO mice (C57BL/6J background, male) were generated by Shanghai Model Organisms Center, Inc. (Shanghai, China).

Techniques: Activation Assay, Fluorescence, Expressing, Clinical Proteomics, Phospho-proteomics, Flow Cytometry

The effect of FGL2 expression on survival and the correlation between FGL2 and immune checkpoints. ( A ) The expression of FGL2 in a human liver tissue microarray was detected by mIHC. Representative images were shown. Scale bar, 20 μm. Kaplan-Meier analysis of overall survival ( B ) and progression-free survival ( C ) of HCC patients based on FGL2 expression ( n = 85). The Gene Expression Profiling Interactive Analysis server was used to analyze the correlation between Fgl2 and Pdcd1 (encoding PD1, ( D ), Cd274 (encoding PD-L1, ( E ), Pdcd1lg2 (encoding PD-L2, ( F ), Ctla4 ( G ), Tigit ( H ), Entpd1 (encoding CD39, ( I ), Havcr2 (encoding TIM3, ( J ), Btla ( K ) and Lag3 ( L ) at the mRNA expression level, respectively. R=Pearson’s correlation coefficient

Journal: Cell Communication and Signaling : CCS

Article Title: Disruption of FGL2 induces TFEB-dependent lysosomal degradation of PD-L1 and enhances the efficacy of anti-PD1 therapy in hepatocellular carcinoma

doi: 10.1186/s12964-026-02704-7

Figure Lengend Snippet: The effect of FGL2 expression on survival and the correlation between FGL2 and immune checkpoints. ( A ) The expression of FGL2 in a human liver tissue microarray was detected by mIHC. Representative images were shown. Scale bar, 20 μm. Kaplan-Meier analysis of overall survival ( B ) and progression-free survival ( C ) of HCC patients based on FGL2 expression ( n = 85). The Gene Expression Profiling Interactive Analysis server was used to analyze the correlation between Fgl2 and Pdcd1 (encoding PD1, ( D ), Cd274 (encoding PD-L1, ( E ), Pdcd1lg2 (encoding PD-L2, ( F ), Ctla4 ( G ), Tigit ( H ), Entpd1 (encoding CD39, ( I ), Havcr2 (encoding TIM3, ( J ), Btla ( K ) and Lag3 ( L ) at the mRNA expression level, respectively. R=Pearson’s correlation coefficient

Article Snippet: Syngeneic Fgl2 gene knockout ( Fgl2 −/− ) mice were constructed by Shanghai Model Organisms Center, Inc. (Shanghai, China).

Techniques: Expressing, Microarray, Gene Expression

FGL2 knockout inhibited tumor growth and downregulated the expression of PD-L1. ( A ) Hepa1-6 cells were inoculated orthotopically into the left liver lobe of WT and Fgl2 -/- mice. The concentration of FGL2 in tumor tissue homogenate was detected by ELISA ( n = 5). ( B ) The livers from C57BL/6 mice bearing orthotopic tumors were shown ( n = 8). ( C ) Representative immunohistochemical images for PD-L1 staining in orthotopic tumors ( n = 4). ( D ) The expression level of PD-L1 on CD45- tumor cells was measured by flow cytometry ( n = 4). Data were represented as median fluorescence intensity (MFI). ( E ) Hepa1-6 cells were inoculated subcutaneously (s.c.) into the right inguinal fold region of WT and Fgl2 -/-mice. The concentration of FGL2 in tumor tissue homogenate was shown ( n = 5). ( F ) Gross images of s.c. tumors of WT or Fgl2 -/- mice ( n = 8). Tumor volume ( G ) and tumor weight ( H ) of the indicated group of C57BL/6 mice ( n = 8). ( I ) The expression level of PD-L1 on tumor cells in the s.c. transplanted hepatomas was detected by flow cytometry ( n = 5). ( J ) WT and Fgl2 -/- mice bearing s.c. tumors were treated with anti-CD3 neutralizing antibodies (200 µg/mice) or IgG1 isotype control (200 µg/mice). Gross images of s.c. tumors in mice treated as indicated ( n = 6). Tumor volume ( K ) and tumor weight ( L ) of the indicated group ( n = 6). Data were presented as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Journal: Cell Communication and Signaling : CCS

Article Title: Disruption of FGL2 induces TFEB-dependent lysosomal degradation of PD-L1 and enhances the efficacy of anti-PD1 therapy in hepatocellular carcinoma

doi: 10.1186/s12964-026-02704-7

Figure Lengend Snippet: FGL2 knockout inhibited tumor growth and downregulated the expression of PD-L1. ( A ) Hepa1-6 cells were inoculated orthotopically into the left liver lobe of WT and Fgl2 -/- mice. The concentration of FGL2 in tumor tissue homogenate was detected by ELISA ( n = 5). ( B ) The livers from C57BL/6 mice bearing orthotopic tumors were shown ( n = 8). ( C ) Representative immunohistochemical images for PD-L1 staining in orthotopic tumors ( n = 4). ( D ) The expression level of PD-L1 on CD45- tumor cells was measured by flow cytometry ( n = 4). Data were represented as median fluorescence intensity (MFI). ( E ) Hepa1-6 cells were inoculated subcutaneously (s.c.) into the right inguinal fold region of WT and Fgl2 -/-mice. The concentration of FGL2 in tumor tissue homogenate was shown ( n = 5). ( F ) Gross images of s.c. tumors of WT or Fgl2 -/- mice ( n = 8). Tumor volume ( G ) and tumor weight ( H ) of the indicated group of C57BL/6 mice ( n = 8). ( I ) The expression level of PD-L1 on tumor cells in the s.c. transplanted hepatomas was detected by flow cytometry ( n = 5). ( J ) WT and Fgl2 -/- mice bearing s.c. tumors were treated with anti-CD3 neutralizing antibodies (200 µg/mice) or IgG1 isotype control (200 µg/mice). Gross images of s.c. tumors in mice treated as indicated ( n = 6). Tumor volume ( K ) and tumor weight ( L ) of the indicated group ( n = 6). Data were presented as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Article Snippet: Syngeneic Fgl2 gene knockout ( Fgl2 −/− ) mice were constructed by Shanghai Model Organisms Center, Inc. (Shanghai, China).

Techniques: Knock-Out, Expressing, Concentration Assay, Enzyme-linked Immunosorbent Assay, Immunohistochemical staining, Staining, Flow Cytometry, Fluorescence, Control

FGL2 upregulated PD-L1 expression in HCC cells and attenuated the cytotoxicity of T cells. Protein levels of FGL2 (FLAG) and PD-L1 were analyzed by Western blot (WB) in Huh7 ( A ) and MHCC97H cells ( B ) stably expressing FGL2-FLAG. Lentivirus expressing shRNA against FGL2 (sh-FGL2) was used for FGL2 knockdown, and nontargeting shRNA(sh-control) was added as control. FGL2 and PD-L1 expression in MHCC97H cells were detected by WB ( C ), immunofluorescence (IF) ( D ) and flow cytometry (FCM) ( E ). Scale bar, 25 μm. FGL2 knockdown or nontargeting shRNA-transfected MHCC97H cells were treated with IFN-γ (50 ng/mL) for 24 h. The expression of PD-L1 was detected by WB ( F ) and FCM ( G ). ( H ) T-cell cytotoxicity assay against MHCC97H cells. Apoptotic MHCC97H cells were detected by FCM. Data were presented as mean ± SEM. * P < 0.05, ** P < 0.01, **** P < 0.0001

Journal: Cell Communication and Signaling : CCS

Article Title: Disruption of FGL2 induces TFEB-dependent lysosomal degradation of PD-L1 and enhances the efficacy of anti-PD1 therapy in hepatocellular carcinoma

doi: 10.1186/s12964-026-02704-7

Figure Lengend Snippet: FGL2 upregulated PD-L1 expression in HCC cells and attenuated the cytotoxicity of T cells. Protein levels of FGL2 (FLAG) and PD-L1 were analyzed by Western blot (WB) in Huh7 ( A ) and MHCC97H cells ( B ) stably expressing FGL2-FLAG. Lentivirus expressing shRNA against FGL2 (sh-FGL2) was used for FGL2 knockdown, and nontargeting shRNA(sh-control) was added as control. FGL2 and PD-L1 expression in MHCC97H cells were detected by WB ( C ), immunofluorescence (IF) ( D ) and flow cytometry (FCM) ( E ). Scale bar, 25 μm. FGL2 knockdown or nontargeting shRNA-transfected MHCC97H cells were treated with IFN-γ (50 ng/mL) for 24 h. The expression of PD-L1 was detected by WB ( F ) and FCM ( G ). ( H ) T-cell cytotoxicity assay against MHCC97H cells. Apoptotic MHCC97H cells were detected by FCM. Data were presented as mean ± SEM. * P < 0.05, ** P < 0.01, **** P < 0.0001

Article Snippet: Syngeneic Fgl2 gene knockout ( Fgl2 −/− ) mice were constructed by Shanghai Model Organisms Center, Inc. (Shanghai, China).

Techniques: Expressing, Western Blot, Stable Transfection, shRNA, Knockdown, Control, Immunofluorescence, Flow Cytometry, Transfection, Cytotoxicity Assay

FGL2 disruption induced lysosome-dependent degradation of PD-L1. HCC cells with FGL2 overexpression ( A ) or knockdown ( B ) were treated with CHX (25 mmol/L) for the indicated time points and then subjected to WB for quantitation of PD-L1 level. The expression of PD-L1 in MHCC97H cells after treatment with proteasome inhibitor (MG132) ( C ) or lysosomal inhibitors, NH4Cl ( D ) and chloroquine ( E ) was detected by WB. ( F ) Images and quantification of LysoTracker red staining in MHCC97H cells were displayed. Scale bar, 100 μm. ( G ) The protein levels of LAMP1 and CTSD were determined by WB. ( H ) The colocalization between PD-L1 and LAMP1 in MHCC97H cells was detected by immunofluorescence assay. The intensity profiles of PD-L1 and LAMP1 along the white line were plotted on the middle panel. The statistical result of the colocalization factor (Pearson’s R value) was shown on the right panel. Scale bar, 25 μm. Data were presented as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Journal: Cell Communication and Signaling : CCS

Article Title: Disruption of FGL2 induces TFEB-dependent lysosomal degradation of PD-L1 and enhances the efficacy of anti-PD1 therapy in hepatocellular carcinoma

doi: 10.1186/s12964-026-02704-7

Figure Lengend Snippet: FGL2 disruption induced lysosome-dependent degradation of PD-L1. HCC cells with FGL2 overexpression ( A ) or knockdown ( B ) were treated with CHX (25 mmol/L) for the indicated time points and then subjected to WB for quantitation of PD-L1 level. The expression of PD-L1 in MHCC97H cells after treatment with proteasome inhibitor (MG132) ( C ) or lysosomal inhibitors, NH4Cl ( D ) and chloroquine ( E ) was detected by WB. ( F ) Images and quantification of LysoTracker red staining in MHCC97H cells were displayed. Scale bar, 100 μm. ( G ) The protein levels of LAMP1 and CTSD were determined by WB. ( H ) The colocalization between PD-L1 and LAMP1 in MHCC97H cells was detected by immunofluorescence assay. The intensity profiles of PD-L1 and LAMP1 along the white line were plotted on the middle panel. The statistical result of the colocalization factor (Pearson’s R value) was shown on the right panel. Scale bar, 25 μm. Data were presented as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Article Snippet: Syngeneic Fgl2 gene knockout ( Fgl2 −/− ) mice were constructed by Shanghai Model Organisms Center, Inc. (Shanghai, China).

Techniques: Disruption, Over Expression, Knockdown, Quantitation Assay, Expressing, Staining, Immunofluorescence

FGL2 disruption promoted the expression of nuclear TFEB. The cytosolic and nuclear distribution of TFEB ( A ) and MITF ( B ) in MHCC97H cells was detected by WB following FGL2 knockdown. Quantification of nuclear TFEB or MITF to Histone-H3 was shown. ( C ) Images and quantification of nuclear TFEB in MHCC97H cells were displayed. Scale bar, 50 μm. The expression levels of TFEB ( D ) and MITF ( E ) were determined by WB in mouse liver cancer tissues ( n = 6). The transcriptional levels of Lamp1, Atp6v0d2 , Ctns and Ctsb were detected by qPCR in mouse liver cancer tissues ( F ) and MHCC97H cells ( G ). TFEB siRNA or control siRNA was transfected to MHCC97H cells pretreated with FGL2 shRNA or control shRNA. The protein levels of LAMP1, CTSD ( H ), and PD-L1 ( I ) were determined by WB. The relative quantification of LAMP1, CTSD or PD-L1 to GAPDH was shown. ( J ) The expression of TFEB in an HCC tissue microarray was detected by mIHC. Representative images were shown. Scale bar, 20 μm. Kaplan-Meier analysis of the progression-free survival ( K ) and overall survival ( L ) of HCC patients based on nuclear TFEB expression ( n = 85). Data were presented as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001

Journal: Cell Communication and Signaling : CCS

Article Title: Disruption of FGL2 induces TFEB-dependent lysosomal degradation of PD-L1 and enhances the efficacy of anti-PD1 therapy in hepatocellular carcinoma

doi: 10.1186/s12964-026-02704-7

Figure Lengend Snippet: FGL2 disruption promoted the expression of nuclear TFEB. The cytosolic and nuclear distribution of TFEB ( A ) and MITF ( B ) in MHCC97H cells was detected by WB following FGL2 knockdown. Quantification of nuclear TFEB or MITF to Histone-H3 was shown. ( C ) Images and quantification of nuclear TFEB in MHCC97H cells were displayed. Scale bar, 50 μm. The expression levels of TFEB ( D ) and MITF ( E ) were determined by WB in mouse liver cancer tissues ( n = 6). The transcriptional levels of Lamp1, Atp6v0d2 , Ctns and Ctsb were detected by qPCR in mouse liver cancer tissues ( F ) and MHCC97H cells ( G ). TFEB siRNA or control siRNA was transfected to MHCC97H cells pretreated with FGL2 shRNA or control shRNA. The protein levels of LAMP1, CTSD ( H ), and PD-L1 ( I ) were determined by WB. The relative quantification of LAMP1, CTSD or PD-L1 to GAPDH was shown. ( J ) The expression of TFEB in an HCC tissue microarray was detected by mIHC. Representative images were shown. Scale bar, 20 μm. Kaplan-Meier analysis of the progression-free survival ( K ) and overall survival ( L ) of HCC patients based on nuclear TFEB expression ( n = 85). Data were presented as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001

Article Snippet: Syngeneic Fgl2 gene knockout ( Fgl2 −/− ) mice were constructed by Shanghai Model Organisms Center, Inc. (Shanghai, China).

Techniques: Disruption, Expressing, Knockdown, Control, Transfection, shRNA, Quantitative Proteomics, Microarray

FGL2 interacted with mTOR kinase and affected the phosphorylation of mTORC1 pathway. ( A ) Immunoblot analysis of (p-)mTOR, (p-)P70S6K, (p-)4EBP1 and (p-)AKT in MHCC97H cells following FGL2 knockdown. ( B ) Total P70S6K, 4EBP1 and AKT proteins as well as their phosphorylated forms were detected in liver cancer tissues from WT and Fgl2 -/- mouse(n = 6). ( C ) The phosphorylation level of TFEB Ser211 was detected by WB. The expression levels of (p-)P70S6K, (p-)4EBP1 ( D ) and PD-L1 ( E ) were detected in MHCC97H cells treated with FGL2 shRNA or control shRNA in the absence or presence of mTOR signaling activator (MHY1485). ( F ) Co-immunoprecipitation analysis of the interaction between FGL2 and mTOR in MHCC97H cells stably expressing FGL2-FLAG. ( G ) The colocalization of FGL2 and mTOR in MHCC97H cells was detected by immunofluorescence. Scale bar, 25 μm.( H ) 293T cells were co-transfected with HA-mTOR, FLAG-FGL2 or vector plasmids. Cell lysates were subjected to co-immunoprecipitation using anti-HA or anti-FLAG antibodies. ( I ) 293T cells were co-transfected with HA-mTOR truncations and FLAG-FGL2 plasmids. Cell lysates were subjected to co-immunoprecipitation using anti-FLAG antibodies. ( J ) MHCC97H cell lysates were subjected to immunoprecipitation with anti-mTOR antibodies, followed by immunoblot analysis. Data were presented as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001

Journal: Cell Communication and Signaling : CCS

Article Title: Disruption of FGL2 induces TFEB-dependent lysosomal degradation of PD-L1 and enhances the efficacy of anti-PD1 therapy in hepatocellular carcinoma

doi: 10.1186/s12964-026-02704-7

Figure Lengend Snippet: FGL2 interacted with mTOR kinase and affected the phosphorylation of mTORC1 pathway. ( A ) Immunoblot analysis of (p-)mTOR, (p-)P70S6K, (p-)4EBP1 and (p-)AKT in MHCC97H cells following FGL2 knockdown. ( B ) Total P70S6K, 4EBP1 and AKT proteins as well as their phosphorylated forms were detected in liver cancer tissues from WT and Fgl2 -/- mouse(n = 6). ( C ) The phosphorylation level of TFEB Ser211 was detected by WB. The expression levels of (p-)P70S6K, (p-)4EBP1 ( D ) and PD-L1 ( E ) were detected in MHCC97H cells treated with FGL2 shRNA or control shRNA in the absence or presence of mTOR signaling activator (MHY1485). ( F ) Co-immunoprecipitation analysis of the interaction between FGL2 and mTOR in MHCC97H cells stably expressing FGL2-FLAG. ( G ) The colocalization of FGL2 and mTOR in MHCC97H cells was detected by immunofluorescence. Scale bar, 25 μm.( H ) 293T cells were co-transfected with HA-mTOR, FLAG-FGL2 or vector plasmids. Cell lysates were subjected to co-immunoprecipitation using anti-HA or anti-FLAG antibodies. ( I ) 293T cells were co-transfected with HA-mTOR truncations and FLAG-FGL2 plasmids. Cell lysates were subjected to co-immunoprecipitation using anti-FLAG antibodies. ( J ) MHCC97H cell lysates were subjected to immunoprecipitation with anti-mTOR antibodies, followed by immunoblot analysis. Data were presented as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001

Article Snippet: Syngeneic Fgl2 gene knockout ( Fgl2 −/− ) mice were constructed by Shanghai Model Organisms Center, Inc. (Shanghai, China).

Techniques: Phospho-proteomics, Western Blot, Knockdown, Expressing, shRNA, Control, Immunoprecipitation, Stable Transfection, Immunofluorescence, Transfection, Plasmid Preparation

FGL2 inhibition enhanced antitumor immune responses of anti-PD1 therapy in HCC. ( A ) WT and Fgl2 -/- mice bearing s.c. tumors were treated with anti-PD1 monoclonal antibodies (αPD1, 100 µg/mice) or IgG isotype control (100 µg/mice). Gross images of tumors in mice treated as indicated ( n = 6). Tumor volume ( B ) and tumor weight ( C ) of the indicated group. ( D ) Representative immunohistochemical images of subcutaneous tumors for PD-L1 staining ( n = 3). Representative flow cytometric plots and quantification of the proportion of IFN-γ+ CD8+ cells ( E ), granzyme B+ CD8+ cells ( F ) and CD107a+ CD8+ cells ( G ) in tumor tissues in response to different treatments. ( H ) Representative flow cytometric plots and quantification of the proportion of Tregs (CD4+ CD25+ Foxp3+) in tumor tissues from the indicated groups. The proportions of Th1 (CD4+ IFN-γ+ T cells) ( I ) and Th2 (CD4+ IL-4+ T cells) cells ( J ) in tumor tissues were shown. Data were presented as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Journal: Cell Communication and Signaling : CCS

Article Title: Disruption of FGL2 induces TFEB-dependent lysosomal degradation of PD-L1 and enhances the efficacy of anti-PD1 therapy in hepatocellular carcinoma

doi: 10.1186/s12964-026-02704-7

Figure Lengend Snippet: FGL2 inhibition enhanced antitumor immune responses of anti-PD1 therapy in HCC. ( A ) WT and Fgl2 -/- mice bearing s.c. tumors were treated with anti-PD1 monoclonal antibodies (αPD1, 100 µg/mice) or IgG isotype control (100 µg/mice). Gross images of tumors in mice treated as indicated ( n = 6). Tumor volume ( B ) and tumor weight ( C ) of the indicated group. ( D ) Representative immunohistochemical images of subcutaneous tumors for PD-L1 staining ( n = 3). Representative flow cytometric plots and quantification of the proportion of IFN-γ+ CD8+ cells ( E ), granzyme B+ CD8+ cells ( F ) and CD107a+ CD8+ cells ( G ) in tumor tissues in response to different treatments. ( H ) Representative flow cytometric plots and quantification of the proportion of Tregs (CD4+ CD25+ Foxp3+) in tumor tissues from the indicated groups. The proportions of Th1 (CD4+ IFN-γ+ T cells) ( I ) and Th2 (CD4+ IL-4+ T cells) cells ( J ) in tumor tissues were shown. Data were presented as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Article Snippet: Syngeneic Fgl2 gene knockout ( Fgl2 −/− ) mice were constructed by Shanghai Model Organisms Center, Inc. (Shanghai, China).

Techniques: Inhibition, Bioprocessing, Control, Immunohistochemical staining, Staining

Schematic of FGL2-mediated PD-L1 regulation and therapy potential of combination interference of FGL2 and PD1. In HCC cells, FGL2 stabilizes the mTOR-Raptor interaction and activates mTORC1 signaling. Activated mTORC1 phosphorylates TFEB, thereby suppressing its nuclear translocation and subsequent lysosomal biogenesis. This lysosomal dysfunction attenuates PD-L1 degradation, leading to elevated PD-L1 abundance and the inhibition of T cell–mediated cytotoxicity. In HCC mouse models, FGL2 inhibition exerts synergistic antitumor effects with anti-PD1 therapy by downregulating tumorous expression of PD-L1, promoting the activity of tumor-infiltrating lymphocytes, and suppressing the accumulation of Tregs

Journal: Cell Communication and Signaling : CCS

Article Title: Disruption of FGL2 induces TFEB-dependent lysosomal degradation of PD-L1 and enhances the efficacy of anti-PD1 therapy in hepatocellular carcinoma

doi: 10.1186/s12964-026-02704-7

Figure Lengend Snippet: Schematic of FGL2-mediated PD-L1 regulation and therapy potential of combination interference of FGL2 and PD1. In HCC cells, FGL2 stabilizes the mTOR-Raptor interaction and activates mTORC1 signaling. Activated mTORC1 phosphorylates TFEB, thereby suppressing its nuclear translocation and subsequent lysosomal biogenesis. This lysosomal dysfunction attenuates PD-L1 degradation, leading to elevated PD-L1 abundance and the inhibition of T cell–mediated cytotoxicity. In HCC mouse models, FGL2 inhibition exerts synergistic antitumor effects with anti-PD1 therapy by downregulating tumorous expression of PD-L1, promoting the activity of tumor-infiltrating lymphocytes, and suppressing the accumulation of Tregs

Article Snippet: Syngeneic Fgl2 gene knockout ( Fgl2 −/− ) mice were constructed by Shanghai Model Organisms Center, Inc. (Shanghai, China).

Techniques: Translocation Assay, Inhibition, Expressing, Activity Assay

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