Journal: Frontiers in Immunology

Article Title: Inhibition of fatty acid-binding protein 4 alleviates psoriasis-like skin inflammation by modulating macrophage polarization

doi: 10.3389/fimmu.2026.1830077

Figure Lengend Snippet: Macrophage polarization imbalance and FABP4 expression in psoriatic skin. (A) Uniform Manifold Approximation and Projection (UMAP) plot of skin myeloid cells grouped into 12 subclusters, each represented with a distinct color. (B) Dot plot showing the expression of representative marker genes for each myeloid subcluster. The color intensity reflects the average expression level, and dot size indicates the percentage of cells expressing each gene. (C) UMAP overlay of M1 and M2 macrophage signature genes in skin myeloid cells ( , ). (D) Bar plot comparing the M2-to-M1 ratio between healthy controls (HC) and psoriasis patients (PSO). A significant decrease in the M2/M1 ratio was observed in PSO, indicating increased M1 polarization (p = 0.0021). (E) The representative immunofluorescence manifestations. Immunostaining analysis revealed distinct FABP4 localization predominantly in dermis of psoriasis skin. Magnified images of the indicated regions are shown. FABP4 is shown in green, CD68 in red, and nuclei are counterstained with DAPI in blue. Yellow arrowheads indicate FABP4 + CD68 + macrophages in human psoriatic skin. n = 3 per group. FABP4, Fatty acid-binding protein 4; DAPI, 4′,6-diamidino-2-phenylindole; HC, Healthy Control; PSO, psoriasis.

Article Snippet: Vehicle and FABP4 inhibitor (0.5 mg/kg and 1 mg/kg; BMS-309403, Medchemexpress LLC, Monmouth Junction, NJ, USA) were administered by intraperitoneal injection into mice on days 2 and 4.

Techniques: Expressing, Marker, Immunofluorescence, Immunostaining, Binding Assay, Control

Journal: Frontiers in Immunology

Article Title: Inhibition of fatty acid-binding protein 4 alleviates psoriasis-like skin inflammation by modulating macrophage polarization

doi: 10.3389/fimmu.2026.1830077

Figure Lengend Snippet: Inhibition of FABP4 attenuates imiquimod-induced psoriasiform skin inflammation in vivo. (A) . Experiment timeline. (B) The representative gross morphology of mice at day 6 (n=5 in each group). (C) The skin inflammation severity index (n=8 in each group). *p < 0.05, **p < 0.01, and ***p < 0.001 compared to the IMQ + Vehicle group for each index on day 6; two-way ANOVA with Tukey’s multiple comparisons test. (D, E) Representative histologic manifestations in back skin and ear skin (H&E staining). Epidermis was lined with yellow and blue dotted line. Epidermal thickening and ear swelling of mouse tissue (n=5 and n=6 spots in each group, respectively). *p < 0.05, **p < 0.01, and ***p < 0.001 compared to the IMQ + Vehicle group; one-way ANOVA with Tukey’s multiple comparisons test. Scale bar: 100 μm. (F) The relative gene expression levels of each inflammatory cytokine gene (n=4 or 5 in each group). IMQ: imiquimod, FABP4 inhibitor: Fatty acid-binding protein 4 inhibitor, il17a, interleukin-17a; il17f, interleukin-17f; il6, interleukin-6; il1β, interleukin-1 beta; tnfα, tumor necrosis factor-alpha.

Article Snippet: Vehicle and FABP4 inhibitor (0.5 mg/kg and 1 mg/kg; BMS-309403, Medchemexpress LLC, Monmouth Junction, NJ, USA) were administered by intraperitoneal injection into mice on days 2 and 4.

Techniques: Inhibition, In Vivo, Staining, Gene Expression, Binding Assay

Journal: Frontiers in Immunology

Article Title: Inhibition of fatty acid-binding protein 4 alleviates psoriasis-like skin inflammation by modulating macrophage polarization

doi: 10.3389/fimmu.2026.1830077

Figure Lengend Snippet: FABP4 inhibition modulates the macrophage polarization in imiquimod-induced psoriasiform mouse model. (A) Representative flow cytometry contour plots showing CD11c + and CD206 + populations within viable CD45 + F4/80 + macrophages isolated from mouse ear skin. CD11c + and CD206 + cells were then quantified within the CD45 + F4/80 + macrophage gate and interpreted as M1-associated/pro-inflammatory and M2-associated macrophage populations, respectively. Quantification was performed using samples from each group (n = 4 per group). (B) Quantitative RT-PCR analysis of M1 macrophage markers (cd11c, mincle and irf5) showing dose-dependent suppression by FABP4 inhibitor treatment. (C) Expression levels of M2 macrophage markers (ym1, arg1 and CD206) demonstrating enhanced M2 polarization following FABP4 inhibition. Data are presented as mean ± SE; *P < 0.05, and ***P < 0.001 compared to the Vehicle. Data were statistically analyzed by one-way ANOVA. FABP4i: Fatty acid-binding protein 4 inhibitor, Mincle: macrophage-inducible C-type lectin, irf5: interferon regulatory factor 5, arg1: arginase 1.

Article Snippet: Vehicle and FABP4 inhibitor (0.5 mg/kg and 1 mg/kg; BMS-309403, Medchemexpress LLC, Monmouth Junction, NJ, USA) were administered by intraperitoneal injection into mice on days 2 and 4.

Techniques: Inhibition, Flow Cytometry, Isolation, Quantitative RT-PCR, Expressing, Binding Assay

Journal: Frontiers in Immunology

Article Title: Inhibition of fatty acid-binding protein 4 alleviates psoriasis-like skin inflammation by modulating macrophage polarization

doi: 10.3389/fimmu.2026.1830077

Figure Lengend Snippet: FABP4 inhibition regulated macrophage polarization in LPS-stimulated macrophages. (A, B) RAW 264.7 macrophages were stimulated with LPS and treated with the FABP4 inhibitor (0.1, 1μM). Quantitative RT-PCR analysis was performed to assess expression of M1-associated genes (cd11c, mincle, iNOS, and irf5) and M2-associated genes (ym1, arg1, cd206 and irf4). (C, D) Representative flow cytometry histograms showing surface expression of CD11c and CD206 in RAW 264.7 macrophages under LPS and FABP4 inhibitor. (E, F) Quantification of CD11c + and CD206 + macrophage populations from three independent experiments. FABP4 inhibition significantly decreased the proportion of CD11c + cells while increasing CD206 + cells compared with LPS treatment alone. (G) RAW 264.7 macrophages were transfected with control or FABP4-specific siRNA and stimulated with LPS. Quantitative RT–PCR analysis of M1-associated genes ( Cd11c, Mincle , and Irf5 ) demonstrated that FABP4 silencing significantly suppressed LPS-induced pro-inflammatory gene expression. (H) Under the same conditions, quantitative RT–PCR analysis of M2-associated genes ( Ym1, Cd206 , and Irf4 ) showed enhanced alternative macrophage polarization following FABP4 knockdown. Data are presented as mean ± SE; *P < 0.05, **P < 0.01, and ***P < 0.001 compared to the Vehicle. Data were statistically analyzed by one-way ANOVA.

Article Snippet: Vehicle and FABP4 inhibitor (0.5 mg/kg and 1 mg/kg; BMS-309403, Medchemexpress LLC, Monmouth Junction, NJ, USA) were administered by intraperitoneal injection into mice on days 2 and 4.

Techniques: Inhibition, Quantitative RT-PCR, Expressing, Flow Cytometry, Transfection, Control, Gene Expression, Knockdown

Journal: Frontiers in Immunology

Article Title: Inhibition of fatty acid-binding protein 4 alleviates psoriasis-like skin inflammation by modulating macrophage polarization

doi: 10.3389/fimmu.2026.1830077

Figure Lengend Snippet: FABP4 regulates macrophage polarization through a PPARG-dependent mechanism. (A) Immunoblot analysis of PPARG protein expression in back skin tissues from imiquimod (IMQ)-treated mice administered vehicle or FABP4 inhibitor as indicated. β-Actin served as a loading control. (B) Densitometric quantification of PPARG protein levels in mouse skin tissue normalized to β-Actin. (C) Macrophages were exposed to an inflammatory cytokine milieu (IL-1β, IL-18 and IL-23) in the presence or absence of the FABP4 inhibitor, followed by immunoblot analysis of PPARG expression. Lamin B was used as a loading control. (D) Quantification of PPARG protein levels normalized to Lamin B from the immunoblot. (E) RAW 264.7 macrophages were stimulated with LPS and treated with a FABP4 inhibitor (0.1 μM or 1 μM) in the presence or absence of the selective PPARG antagonist GW9662, as indicated. After 24 h, mRNA expression levels of M2-associated genes (Arg1, Irf4, and Ym1) were analyzed by quantitative RT–PCR. Data are presented as mean ± SE; *P < 0.05, **P < 0.01, and ***P < 0.001 compared to the Vehicle. Data were statistically analyzed by one-way ANOVA.

Article Snippet: Vehicle and FABP4 inhibitor (0.5 mg/kg and 1 mg/kg; BMS-309403, Medchemexpress LLC, Monmouth Junction, NJ, USA) were administered by intraperitoneal injection into mice on days 2 and 4.

Techniques: Western Blot, Expressing, Control, Quantitative RT-PCR

Journal: Frontiers in Immunology

Article Title: Inhibition of fatty acid-binding protein 4 alleviates psoriasis-like skin inflammation by modulating macrophage polarization

doi: 10.3389/fimmu.2026.1830077

Figure Lengend Snippet: Schematic illustration of FABP4-mediated immune modulation in psoriasis skin inflammation. In psoriatic skin, elevated FABP4 expression in infiltrating macrophages promotes proinflammatory M1 polarization and suppresses PPARG activity. Pharmacological inhibition of FABP4 restores PPARG protein stability and activity, thereby shifting macrophage polarization toward an anti-inflammatory M2 phenotype. The increased expression of M2-associated markers (Arg1, CD206, Irf4) promotes the resolution of inflammation and alleviates psoriasis-like skin pathology. This schematic summarizes the FABP4–PPARG axis as a key regulatory pathway controlling macrophage polarization in psoriatic inflammation.

Article Snippet: Vehicle and FABP4 inhibitor (0.5 mg/kg and 1 mg/kg; BMS-309403, Medchemexpress LLC, Monmouth Junction, NJ, USA) were administered by intraperitoneal injection into mice on days 2 and 4.

Techniques: Expressing, Activity Assay, Inhibition

Journal: Cancer Immunology, Immunotherapy : CII

Article Title: Promoting APC function of B cells via reprogramming the fatty acid metabolism enhances anticancer immunity in metastatic ovarian cancer

doi: 10.1007/s00262-026-04387-y

Figure Lengend Snippet: The APC function and resulting anticancer immunity of B cells can be enhanced by oleic acid (OA) via reprogramming FA metabolism in vitro. A Mean fluorescence intensity of CD80 and MHC Class II molecules in CD19 + B cells from peripheral blood of healthy volunteers (n = 3) treated with OA and PA (both 150 μM), respectively. B Mean fluorescence intensity of CD80, CD86, CD83, MHC Class II molecules, and Ki67 in splenic CD19 + B cells of WT mice treated with 150 μM OA. C Mean fluorescence intensity of CD80, CD86, CD83, and MHC Class II molecules in ascitic CD19 + B cells from 3 w OvCa-bearing mice when treated with 150 μM OA. D Analysis of FA metabolism-related signaling pathways based on RNA-seq results. GSEA was used to analysised the FA metabolic pathways. E Comparison of mRNA levels of main FA metabolic genes in ascitic B cells from 3 w tumor-bearing mice when treated with 150 μM OA. The relative expression of each gene was calculated using β -actin as the internal reference. F Experimental scheme to detect the influence of inhibiting OA uptake on ascitic B cells. G Comparison of protein expressions of main FA metabolic molecules in 3 w OvCa-bearing mouse ascitic B cells pretreated with BMS and treated with OA. β -Actin was used as the internal control to calculate the relative expression level of the main FA metabolic molecules. H Mean fluorescence intensity of Bodipy C16 in 3 w OvCa-bearing mouse ascitic B cells pretreated with BMS and treated with OA was detected by flow cytometry. I The expression of A-CoA, ATP and the FAO activity in 3 w OvCa-bearing mouse ascitic B cells pretreated with BMS treated with OA was detected by ELISA. J Mean fluorescence intensity of intracellular oxidized lipid in 3 w OvCa-bearing mouse ascitic B cells pretreated with BMS and treated with OA was detected by flow cytometry. K Mean fluorescence intensity of CD80, CD86, and CD83 in 3 w OvCa-bearing mouse ascitic CD19 + B cells pretreated with BMS and treated with OA was detected by flow cytometry. L Mean fluorescence intensity of Bodipy C16, CD80, CD86 and CD83 in FABP4-knockdown CD19 + B cells, which are from the ascites of 3 w OvCa-bearing mice, treated with OA, was detected by flow cytometry. PBMC, peripheral blood mononuclear cell; SP, spleen; AS, Ascites; OA, oleic acid; PA, palmitic acid; BMS, BMS309403. Data are presented as the mean ± SD of three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns, not significant

Article Snippet: In the mechanistic study, mouse ascitic CD19 + B cells (1 × 10 6 /ml) were pretreated with fatty acid binding protein 4 gene (FABP4) inhibitor (BMS309403, MedChemExpress; Cat# HY-101903; 50 μM), PPARγ antagonist (GW9662, MedChemExpress; Cat# HY-16578; 25 μM), and PPAR γ agonist (Troglitazone, Trog, MedChemExpress; Cat# HY-50935; 10 μM) for 2h, respectively.

Techniques: In Vitro, Fluorescence, Protein-Protein interactions, RNA Sequencing, Comparison, Expressing, Control, Flow Cytometry, Activity Assay, Enzyme-linked Immunosorbent Assay, Knockdown

Journal: Cancer Immunology, Immunotherapy : CII

Article Title: Promoting APC function of B cells via reprogramming the fatty acid metabolism enhances anticancer immunity in metastatic ovarian cancer

doi: 10.1007/s00262-026-04387-y

Figure Lengend Snippet: The enhanced APC function of B cells by OA in vitro is achieved through H3K27ac-mediated upregulation of PPAR γ expression. A Protein expression of β -actin and H3K27ac in 3 w OvCa-bearing mouse ascitic CD19 + B cells pretreated with BMS and treated with OA was assessed by WB. β -Actin was used as the internal control to calculate the relative expression level of H3K27ac. B The enrichment percentage of H3K27ac at the PPAR γ , CD80, CD86, and CD83 promoter regions was quantified using ChIP-seq analysis. C Correlation analysis of PPAR γ and APC function-related genes (CD80, CD86, CD83, MHC II) in B cells in OvCa patients in the TCGA database (n = 426). D Analysis of protein interaction among FABP4, PPAR γ , CD80, CD86, and CD83. E The enrichment percentage of PPAR γ at the CD80, CD86, and CD83 promoter regions was quantified using ChIP-seq analysis. F Mean fluorescence intensity of CD80, CD86, and CD83 in 3 w OvCa-bearing mouse ascitic CD19 + B cells pretreated with BMS, GW9662/Trog, and treated with OA was detected by flow cytometry. AS, Ascites; Ag, Antigen; OA, oleic acid; BMS, BMS309403. Data are presented as the mean ± SD of three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns, not significant

Article Snippet: In the mechanistic study, mouse ascitic CD19 + B cells (1 × 10 6 /ml) were pretreated with fatty acid binding protein 4 gene (FABP4) inhibitor (BMS309403, MedChemExpress; Cat# HY-101903; 50 μM), PPARγ antagonist (GW9662, MedChemExpress; Cat# HY-16578; 25 μM), and PPAR γ agonist (Troglitazone, Trog, MedChemExpress; Cat# HY-50935; 10 μM) for 2h, respectively.

Techniques: In Vitro, Expressing, Control, ChIP-sequencing, Fluorescence, Flow Cytometry