agonist antibody to the 4-1bb co-stimulatory receptor anti-mouse 41bb rigg1 clone lob12.3  (Bio X Cell)

Journal: Signal Transduction and Targeted Therapy

Article Title: Dual targeting PD-L1 and 4-1BB to overcome dendritic cell-mediated lenalidomide resistance in follicular lymphoma

doi: 10.1038/s41392-024-02105-7

Figure Lengend Snippet: PU.1 modulated PD-1/PD-L1 and 4-1BB/4-1BBL-mediated FL cell interaction with cDC1. a Immune checkpoints with differential expression between the cDC1 high and low groups identified by RNA sequencing. b Correlation between PU.1 and PD-L1, as well as PU.1 and 4-1BBL expression calculated by Pearson correlation coefficient analysis. c Relative luciferase activities in PD-L1 WT or PD-L1 MUT transfected HEK-293T cells, SC1 cells, DOHH2 cells were detected. Mean with SD was presented ( n = 3). d Relative luciferase activities in 4-1BBL WT or 4-1BBL MUT transfected HEK-293T cells, SC1 cells, DOHH2 cells were detected. Mean with SD was presented ( n = 3). e Western blot of PU.1, PD-L1, and 4-1BBL expression in the SpCas9-PU.1 transfected SC1 cells and pGMLV-PU.1 transfected DOHH2 cells

Article Snippet: For PD-L1 and 4-1BB antibody treatment, each mouse received an injection of 200 μg anti-mouse 4-1BB agonistic antibody (BE0296, Bioxcell, Lebanon, USA) and anti-mouse PD-L1 antibody (BE0101, Bioxcell) via the tail vein, three times each week for 2 weeks.

Techniques: Expressing, RNA Sequencing Assay, Luciferase, Transfection, Western Blot

Journal: Signal Transduction and Targeted Therapy

Article Title: Dual targeting PD-L1 and 4-1BB to overcome dendritic cell-mediated lenalidomide resistance in follicular lymphoma

doi: 10.1038/s41392-024-02105-7

Figure Lengend Snippet: Dual targeting PD-L1 and 4-1BB counteracted PU.1-mediated cDC1 alterations in vitro . a Cell growth of the SpCas9-PU.1-transfected SC1 co-culture system, treated with or without the bi-specific PD-L1/4-1BB antibody assessed by MTT assay. Mean with SD was presented ( n = 5). b cDC1 absolute cell numbers in the SpCas9-PU.1 transfected SC1 co-culture system treated with or without bi-specific PD-L1/4-1BB antibody assessed by flow cytometry. Mean with SD was presented ( n = 3). c cDC1 maturation in the SpCas9-PU.1 transfected SC1 co-culture system treated with or without bi-specific PD-L1/4-1BB antibody assessed by flow cytometry. Mean with SD was presented ( n = 3). d cDC1 endocytic activity in the SpCas9-PU.1 transfected SC1 co-culture system treated with or without bi-specific PD-L1/4-1BB antibody assessed by flow cytometry. Mean with SD was presented ( n = 3). e LC3B expression in the SpCas9-PU.1 transfected SC1 co-culture system treated with or without bi-specific PD-L1/4-1BB antibody. Mean with SD was presented ( n = 3). f Typical autophagosomes in the SpCas9-PU.1-transfected SC1 co-culture system, with or without bi-specific PD-L1/4-1BB antibody treatment assessed by transmission electron microscope. Cells were counted from randomly selected fields ( n = 5). Mean with SD was presented

Article Snippet: For PD-L1 and 4-1BB antibody treatment, each mouse received an injection of 200 μg anti-mouse 4-1BB agonistic antibody (BE0296, Bioxcell, Lebanon, USA) and anti-mouse PD-L1 antibody (BE0101, Bioxcell) via the tail vein, three times each week for 2 weeks.

Techniques: In Vitro, Transfection, Co-Culture Assay, MTT Assay, Flow Cytometry, Activity Assay, Expressing, Transmission Assay, Microscopy

Journal: Signal Transduction and Targeted Therapy

Article Title: Dual targeting PD-L1 and 4-1BB to overcome dendritic cell-mediated lenalidomide resistance in follicular lymphoma

doi: 10.1038/s41392-024-02105-7

Figure Lengend Snippet: Combined treatment of PD-L1 and 4-1BB antibody exhibited in vivo anti-lymphoma activity on PU.1-altered murine xenograft model. a SpCas9-scramble and SpCas9-PU.1 cells were injected subcutaneously treated with or without lenalidomide, or co-treated with PD-L1 and 4-1BB antibody. Tumor size was measured. Mean with SD was presented ( n = 3). b Standardized uptake value intensity in SpCas9-scramble group and SpCas9-PU.1 group treated with or without lenalidomide, or co-treated with PD-L1 and 4-1BB antibody assessed by Micro PET-CT. c , d cDC1 maturation in SpCas9-scramble group and SpCas9-PU.1 group treated with or without lenalidomide, or co-treated with PD-L1 and 4-1BB antibody assessed by flow cytometry. Mean with SD was presented ( n = 3). e Flow cytometry analysis of cDC1 endocytic activity in SpCas9-scramble group and SpCas9-PU.1 group treated with or without lenalidomide, or co-treated with PD-L1 and 4-1BB antibody. Mean with SD was presented ( n = 3). f Typical autophagosomes in the SpCas9-scramble group and SpCas9-PU.1 group, with or without lenalidomide treatment, or co-treated with PD-L1 and 4-1BB antibody assessed by transmission electron microscopy. Cells were counted from randomly selected fields ( n = 5). Mean with SD was presented

Article Snippet: For PD-L1 and 4-1BB antibody treatment, each mouse received an injection of 200 μg anti-mouse 4-1BB agonistic antibody (BE0296, Bioxcell, Lebanon, USA) and anti-mouse PD-L1 antibody (BE0101, Bioxcell) via the tail vein, three times each week for 2 weeks.

Techniques: In Vivo, Activity Assay, Injection, Micro-PET, Flow Cytometry, Transmission Assay, Electron Microscopy

Journal: bioRxiv

Article Title: An amphiregulin reporter mouse enables transcriptional and clonal expansion analysis of reparative lung Treg cells

doi: 10.1101/2024.09.26.615245

Figure Lengend Snippet: A) “Immunosuppression” and “Tissue repair” modules of genes (Treg-specific), established from literature. B) “Immunosuppression” and “Tissue repair” module scores were calculated for cells in the Ccr8 subgroup of each treatment dataset, then plotted against each other. C) Left: Subclusters with differing patterns of module expression are indicated by boxes on plot. Middle: Volcano plots of DEGs between groups indicated at left for each treatment dataset. Red dots: significantly differentially expressed (FDR adj. p-value < 0.05). No fold change cutoff. Genes encoding receptors of interest for activation of tissue repair function are indicated on graphs and in the summary on the right. D) Flow cytometric profiling of lung Treg cells from bleomycin-treated lung tissue (11-15 dpi), for receptors identified in (C). E) Experimental schematic of Col14-LMC and Treg cell co-culture. F) qPCR for Treg cell-induced genes Lif and Il6 in Col14-LMC following lung or spleen Treg cell co-culture, with or without αCD3/CD28 beads for T cell activation as indicated. G) qPCR for Lif and Il6 in Col14-LMC following Treg cell co-culture, with control IgG or αAREG antibody. H) qPCR for Lif and Il6 in Col14-LMC following Treg cell direct co-culture, or separation with a 0.4 µm transwell insert. I) qPCR for Lif and Il6 in Col14-LMC following Treg cell co-culture, with vehicle or rmIL-18. J) qPCR for Lif and Il6 in Col14-LMC following Treg cell co-culture, with vehicle or a combination of rm4-1BB ligand, vitronectin, and leukotriene B4. K) qPCR for Lif and Il6 in Col14-LMC following Treg cell co-culture, with control IgG or αOX-40 activating antibody (clone OX-86). L) qPCR for Lif and Il6 in Col14-LMC following Treg cell co-culture, with control IgG or α4-1BB activating antibody (clone 3H3). Standard error displayed on graphs; n.s: not significant, *: 0.01

Article Snippet: For some experiments, InVivoMAB anti-mouse 4-1BB agonistic antibody (clone 3H3; BioXCell) (10 µg/ml) or Rat IgG2a, κ Isotype Control (Biolegend) (10 µg/ml) was added to co-cultures.

Techniques: Expressing, Activation Assay, Co-Culture Assay, Control

Journal: Cancer Immunology, Immunotherapy

Article Title: Anti-tumor effects of RTX-240: an engineered red blood cell expressing 4-1BB ligand and interleukin-15

doi: 10.1007/s00262-021-03001-7

Figure Lengend Snippet: 4-1BBL and IL-15TP on RTX-240 stimulate receptor-specific activation in reporter cells. a Representative flow cytometry plots of RTX-240 stained for 4-1BBL and IL-15TP. b Fold change in NFkB activation in 4-1BB/NFkB reporter HEK293 cells incubated with engineered RBCs or 4-1BB agonistic antibody + cross-linking antibody (10 nM and 1 nM agonist with 25 nM and 2.5 nM cross-linker, respectively) compared with media alone. c Fold change in JAK/STAT activation by IL-15 in reporter HEK-Blue-IL-2 cells incubated with engineered RBCs or recombinant (r) IL-15 (threefold dilutions from 100 pg/mL), compared with media alone. Bars indicate SD of 2–3 technical replicates. IL-15TP, trans-presented interleukin 15; RBC, red blood cell; SD, standard deviation

Article Snippet: The murine melanoma cell line B16-F10 (ATCC) was cultured according to ATCC recommendations and 1 × 10 5 cells were injected IV in 200 μL RPMI-1640 into C57BL/6 mice to establish a pulmonary metastatic melanoma model. On days 1, 5, and 8 post-inoculation, animals received either 1 × 10 9 mRBCs IV, 4-1BB agonistic antibody (InVivoMab™ anti-mouse 4-1BB clone 3H3, Bio X Cell, Inc., 2.5 mg/kg) intraperitoneally (IP), or rIL-15 (0.2 mg/kg) IP.

Techniques: Activation Assay, Flow Cytometry, Staining, Incubation, Recombinant, Standard Deviation

Journal: Cancer Immunology, Immunotherapy

Article Title: Anti-tumor effects of RTX-240: an engineered red blood cell expressing 4-1BB ligand and interleukin-15

doi: 10.1007/s00262-021-03001-7

Figure Lengend Snippet: Direct activation of CD8 + T cells and NK cells in vitro. ( a i) PBMCs were labeled with CTFR and incubated with the indicated treatments for 8 days, then analyzed by flow cytometry for: a memory CD8 + T cell numbers; b memory CD8 + T cell proliferation (percentage of cells that went through at least one division); c CD8 + effector memory differentiation; d NK cell numbers; e NK cell proliferation (percentage of cells that went through at least one division); f – i expression of the following molecules on NK cells: f TRAIL, g NKp44, h Granzyme B and i 4-1BB. j Purified NK cells were incubated in vitro overnight with the indicated treatments, then incubated with labeled K562 target cells for 4 h. Target cell killing was measured by flow cytometry. Bars indicate a – i SD of 3 biological replicates j or SD of 3 technical replicates. Flow plots are representative data from one donor. CTFR, CellTrace Far Red dye; GzmB, Granzyme B; IL-15TP, trans-presented interleukin-15; NK, natural killer; PBMC, peripheral blood mononuclear cell; rIL-15, recombinant IL-15; SD, standard deviation

Article Snippet: The murine melanoma cell line B16-F10 (ATCC) was cultured according to ATCC recommendations and 1 × 10 5 cells were injected IV in 200 μL RPMI-1640 into C57BL/6 mice to establish a pulmonary metastatic melanoma model. On days 1, 5, and 8 post-inoculation, animals received either 1 × 10 9 mRBCs IV, 4-1BB agonistic antibody (InVivoMab™ anti-mouse 4-1BB clone 3H3, Bio X Cell, Inc., 2.5 mg/kg) intraperitoneally (IP), or rIL-15 (0.2 mg/kg) IP.

Techniques: Activation Assay, In Vitro, Labeling, Incubation, Flow Cytometry, Expressing, Purification, Recombinant, Standard Deviation

Journal: Cancer Immunology, Immunotherapy

Article Title: Anti-tumor effects of RTX-240: an engineered red blood cell expressing 4-1BB ligand and interleukin-15

doi: 10.1007/s00262-021-03001-7

Figure Lengend Snippet: mRBC-240 is tolerated in mice. a Quantification of liver macrophages (F4/80 +). b Representative images of IHC staining of macrophages (F4/80) from selected mice. c Quantification of liver-infiltrating CD8 + T cells and d liver-infiltrating cytotoxic CD8 + T cells (CD8 + /Eomes + /KLRG1 +). Quantification was performed on liver samples of C57BL/6 wild-type mice by flow cytometry on day 18 following 4 doses of either mRBC-240 (1 × 10 9 , 3 × 10 8 , or 1 × 10 8 ), mRBC-CTRL, 4-1BB agonistic antibody (10 mg/kg or 2.5 mg/kg) ( n = 8 mice/group) or PBS. e ALT liver enzyme levels (U/L) in serum on day 18. f Inflammation scoring performed on H&E stained liver sections. g Representative images of H&E staining of liver sections from selected mice. All comparisons were analyzed by a one-way ANOVA and compared with control groups and showing as * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. ALT, alanine aminotransferase; IHC, immunohistochemistry; H&E, hematoxylin and eosin; mRBC, mouse red blood cell; PBS, phosphate-buffered saline

Article Snippet: The murine melanoma cell line B16-F10 (ATCC) was cultured according to ATCC recommendations and 1 × 10 5 cells were injected IV in 200 μL RPMI-1640 into C57BL/6 mice to establish a pulmonary metastatic melanoma model. On days 1, 5, and 8 post-inoculation, animals received either 1 × 10 9 mRBCs IV, 4-1BB agonistic antibody (InVivoMab™ anti-mouse 4-1BB clone 3H3, Bio X Cell, Inc., 2.5 mg/kg) intraperitoneally (IP), or rIL-15 (0.2 mg/kg) IP.

Techniques: Immunohistochemistry, Flow Cytometry, Staining

Journal: Frontiers in Immunology

Article Title: 4-1BB Signaling Promotes Alveolar Macrophages-Mediated Pro-Fibrotic Responses and Crystalline Silica-Induced Pulmonary Fibrosis in Mice

doi: 10.3389/fimmu.2018.01848

Figure Lengend Snippet: Sequences.

Article Snippet: Agonist 4-1BB mAb (10 μg/mL; cat: MAB9371, R&D Systems, Minneapolis, MN, USA) ( ) was used to detect the effect of 4-1BB signaling on macrophages 2 h before CS exposure.

Techniques:

Journal: Frontiers in Immunology

Article Title: 4-1BB Signaling Promotes Alveolar Macrophages-Mediated Pro-Fibrotic Responses and Crystalline Silica-Induced Pulmonary Fibrosis in Mice

doi: 10.3389/fimmu.2018.01848

Figure Lengend Snippet: Activation of 4-1BB signaling promotes the secretion of pro-fibrotic mediators by MH-S cells. MH-S cells treated with or without agonist 4-1BB mAb (10 µg/mL) or IgG (10 µg/mL) for 2 h prior to exposure to crystalline silica (50 µg/cm 2 ) for 12 h. (A) Western blots analysis of ASK-1 and downstream mitogen-activated protein kinase proteins (p38 and JNK/stress activated protein kinase) and their phosphorylated forms. (B–D) The levels of phospho-ASK1, phospho-p38, and phospho-JNK were normalized to those of β-actin ( n = 3). (E) Western blots analysis of IκBα and phospho-IκBα. (F) The level of phospho-IκBα was normalized to those of β-actin ( n = 3). (G–I) Real-time polymerase chain reaction analysis of MMP12, MMP9, and monocyte chemoattractant protein-1 mRNA expression ( n = 4). (J–L) ELISA analysis was used to quantify the secretion of IL-1β, IL-6 and tumor necrosis factor-α ( n = 4). The results were representative of three independent experiments. Results were graphed as the mean ± SEM (* p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001).

Article Snippet: Agonist 4-1BB mAb (10 μg/mL; cat: MAB9371, R&D Systems, Minneapolis, MN, USA) ( ) was used to detect the effect of 4-1BB signaling on macrophages 2 h before CS exposure.

Techniques: Activation Assay, Western Blot, Real-time Polymerase Chain Reaction, Expressing, Enzyme-linked Immunosorbent Assay

Journal: Frontiers in Immunology

Article Title: 4-1BB Signaling Promotes Alveolar Macrophages-Mediated Pro-Fibrotic Responses and Crystalline Silica-Induced Pulmonary Fibrosis in Mice

doi: 10.3389/fimmu.2018.01848

Figure Lengend Snippet: Blockade of 4-1BB signaling attenuates the secretion of pro-fibrotic mediators by MH-S cells. Transfected (Len-cont. and sh-4-1BB) MH-S cells were treated with or without NQDI 1 (10 µM), 4-1BBIg (10 µg/mL), or IgG1 (10 µg/mL) for 2 h, then exposed to crystalline silica (50 µg/cm 2 ) for 12 h. (A) Western blots analysis of ASK-1 and downstream mitogen-activated protein kinase proteins (p38 and JNK/stress activated protein kinase) and their phosphorylated forms. (B–D) Levels of phospho-ASK1, phospho-p38, and phospho-JNK were normalized to those of β-actin ( n = 3). (E,G) Western blots analysis of IκBα and phospho-IκBα. (F,H) The level of phospho-IκBα was normalized to those of β-actin ( n = 3). (I–K) The expressions of MMP12, MMP9, and monocyte chemoattractant protein-1 were detected by real-time polymerase chain reaction analysis ( n = 4). ELISA analysis of cytokines in the culture supernatants. (L) IL-1β, (M) IL-6, (N) tumor necrosis factor-α ( n = 4). Data were shown as mean ± SEM (* p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001; ns, not significant). The data were representative of three independent experiments.

Article Snippet: Agonist 4-1BB mAb (10 μg/mL; cat: MAB9371, R&D Systems, Minneapolis, MN, USA) ( ) was used to detect the effect of 4-1BB signaling on macrophages 2 h before CS exposure.

Techniques: Transfection, Western Blot, Real-time Polymerase Chain Reaction, Enzyme-linked Immunosorbent Assay

Journal: Frontiers in Immunology

Article Title: 4-1BB Signaling Promotes Alveolar Macrophages-Mediated Pro-Fibrotic Responses and Crystalline Silica-Induced Pulmonary Fibrosis in Mice

doi: 10.3389/fimmu.2018.01848

Figure Lengend Snippet: Expression of 4-1BB (CD137) and 4-1BBL (CD137L) on pulmonary macrophages. After 7-days exposure to crystalline silica, mice were sacrificed. The lungs were prepared as single-cell suspensions for flow cytometric analyses ( n = 3–4). (A) Representative plots of flow cytometric analyses for 4-1BB and 4-1BBL on alveolar macrophages (AMs) and interstitial macrophages (IMs). (B,C) The percentage of AMs expressing 4-1BB and 4-1BBL. (D,E) The frequency of AMs and IMs in CD45+ cells from the lungs. (F,G) The percentage of IMs expressing 4-1BB and 4-1BBL. The experiments were performed twice with similar results. Data were shown as mean ± SEM (* p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001; ns, not significant).

Article Snippet: Agonist 4-1BB mAb (10 μg/mL; cat: MAB9371, R&D Systems, Minneapolis, MN, USA) ( ) was used to detect the effect of 4-1BB signaling on macrophages 2 h before CS exposure.

Techniques: Expressing

Journal: Frontiers in Immunology

Article Title: 4-1BB Signaling Promotes Alveolar Macrophages-Mediated Pro-Fibrotic Responses and Crystalline Silica-Induced Pulmonary Fibrosis in Mice

doi: 10.3389/fimmu.2018.01848

Figure Lengend Snippet: Expression of 4-1BB on CD4+ T cells. (A) Representative plots of flow cytometric analyses for 4-1BB on effector and naïve T cells. (B) The percentage of effector T cells expressing 4-1BB. (C,D) The frequency of effector and naïve T cells in CD4+ T cells from the lungs. (E) The percentage of naïve T cells expressing 4-1BB. The experiments were performed twice with similar results. Data were shown as mean ± SEM (* p ≤ 0.05; ** p ≤ 0.01; ns, not significant).

Article Snippet: Agonist 4-1BB mAb (10 μg/mL; cat: MAB9371, R&D Systems, Minneapolis, MN, USA) ( ) was used to detect the effect of 4-1BB signaling on macrophages 2 h before CS exposure.

Techniques: Expressing

Journal: Frontiers in Immunology

Article Title: 4-1BB Signaling Promotes Alveolar Macrophages-Mediated Pro-Fibrotic Responses and Crystalline Silica-Induced Pulmonary Fibrosis in Mice

doi: 10.3389/fimmu.2018.01848

Figure Lengend Snippet: 4-1BB expression on the mouse alveolar macrophage cell line, MH-S. MH-S cells were treated with crystalline silica (50 µg/cm 2 ) or saline for 12 h. (A,B) The percentage of MH-S cells expressing 4-1BB ( n = 4). (C) Western blot analysis of 4-1BB protein from whole cell lysates. (D) Quantification of the 4-1BB protein level relative to that of β-actin is shown ( n = 3). (E) Total RNA was isolated to analyze 4-1BB mRNA expression ( n = 4) relative to GAPDH. The data were representative of three independent experiments. Data were expressed as mean ± SEM (*** p ≤ 0.001).

Article Snippet: Agonist 4-1BB mAb (10 μg/mL; cat: MAB9371, R&D Systems, Minneapolis, MN, USA) ( ) was used to detect the effect of 4-1BB signaling on macrophages 2 h before CS exposure.

Techniques: Expressing, Saline, Western Blot, Isolation

Journal: Frontiers in Immunology

Article Title: 4-1BB Signaling Promotes Alveolar Macrophages-Mediated Pro-Fibrotic Responses and Crystalline Silica-Induced Pulmonary Fibrosis in Mice

doi: 10.3389/fimmu.2018.01848

Figure Lengend Snippet: The secretion of pro-fibrotic mediators is reduced in the lungs from crystalline silica (CS)-injured mice, upon inhibition of 4-1BB signaling. C57BL/6 mice were administered a CS suspension or saline, respectively; 4-1BBIg or isotype control (IgG1) were injected intraperitoneally (i.p.; n = 3–4). (A–D) Quantification of MMP9 and MMP12 protein levels by western blot, which were normalized to those of β-actin in lungs. Shown as bar graph. (E–H) ELISA analysis of cytokines in lung tissues. (E) IL-1β, (F) IL-6, (G) tumor necrosis factor-α, (H) monocyte chemoattractant protein-1. Experiments were performed three times. C57BL/6 mice were administered a CS suspension or saline, respectively; NQDI 1 or isotype control were injected i.p. ( n = 10). (I) Immunohistochemical staining of paraffin-embedded lung tissue sections at 7 and 56 days showed CD68, MMP9, and MMP12 expression. Nuclei were stained by hematoxylin (blue). (J–L) Identification of MMP9 and MMP12 protein levels in mouse lung tissues at 7 and 56 days by western blot. The levels of MMP9 and MMP12 were normalized to those of β-actin. (M) Representative images for the immunohistochemical staining of collagen I in paraffin-embedded lung tissue sections 56 days after CS instillation. Nuclei were stained by hematoxylin (blue). (I,M) Scale bar, 50 µm. Experiments were performed three times. Data are shown as mean ± SEM (* p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.001; ns, not significant).

Article Snippet: Agonist 4-1BB mAb (10 μg/mL; cat: MAB9371, R&D Systems, Minneapolis, MN, USA) ( ) was used to detect the effect of 4-1BB signaling on macrophages 2 h before CS exposure.

Techniques: Inhibition, Suspension, Saline, Control, Injection, Western Blot, Enzyme-linked Immunosorbent Assay, Immunohistochemical staining, Staining, Expressing

Journal: Frontiers in Immunology

Article Title: 4-1BB Signaling Promotes Alveolar Macrophages-Mediated Pro-Fibrotic Responses and Crystalline Silica-Induced Pulmonary Fibrosis in Mice

doi: 10.3389/fimmu.2018.01848

Figure Lengend Snippet: A model for alveolar macrophages (AMs) expressing 4-1BB in the regulation of pulmonary fibrosis through secreting pro-fibrotic mediators. The expression of 4-1BB increases in AMs in response to crystalline silica, which leads to elevated secretion of pro-inflammatory and pro-fibrotic cytokines, chemokines, and MMPs. These pro-fibrotic mediators promote pulmonary alveoli injury, the accumulation of monocytes, lymphocytes, and fibrocytes, and collagen deposition, resulting in pulmonary fibrosis.

Article Snippet: Agonist 4-1BB mAb (10 μg/mL; cat: MAB9371, R&D Systems, Minneapolis, MN, USA) ( ) was used to detect the effect of 4-1BB signaling on macrophages 2 h before CS exposure.

Techniques: Expressing