{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen L"],"funding":["Jiangsu Provincial Medical Key Discipline","Changzhou Science and Technology Support Program","the Leading Talent of Changzhou“The 14th Five-Year Plan” High-Level Health Talents Training Project","Changzhou Science and Technology Project (Applied Based Research)","the National Natural Science Foundation of China","the Key R&D Project of Jiangsu Province","Changzhou Science and Technology Project","the Leading Talent of Changzhou\"The 14th Five-Year Plan\" High-Level Health Talents Training Project","Changzhou Medical Center of Nanjing Medical University","the Key R&amp;D Project of Jiangsu Province","Changzhou Clinical Medical Center","Prospective Research Program of Changzhou Xitaihu Development Foundation For Frontier Cell-Therapeutic Technology","Provincial-level Talent Program for National Center of Technology Innovation for Biopharmaceuticals"],"pagination":["25"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12801534"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(1)"],"pubmed_abstract":["<h4>Background</h4>Cancer-associated fibroblasts (CAFs) are key regulators in tumor microenvironment and tumor immunity, partly through MHC-II expression that modulates T-cell differentiation. However, the upstream cytokine signals controlling MHC-II expression in fibroblasts still remain poorly defined.<h4>Methods</h4>We examined MHC-II expression on fibroblasts under stimulation with interferon-γ (IFN-γ) and interleukin-1β (IL-1β) by using flow cytometry, transcriptomic analysis, and qRT-PCR. To dissect transcriptional regulation, we generated CIITA-overexpressing and CIITA-deficient fibroblast lines by lentiviral transduction and CRISPR/Cas9-mediated editing. Public scRNA-seq, ATAC-seq, and ChIP-seq datasets were further analyzed to validate molecular mechanisms.<h4>Results</h4>IFN-γ robustly up-regulated MHC-II expression on fibroblasts, while IL-1β selectively suppressed this induction without affecting PD-L1. Mechanistically, IL-1β attenuated IFN-γ-induced CIITA expression at the mRNA level but did not alter STAT1 abundance or phosphorylation. Functional assays confirmed that CIITA was indispensable for IFN-γ-driven MHC-II expression in fibroblasts. Integration of transcriptomic and epigenomic data demonstrated that CIITA directly bound MHC-II gene promoters and regulated chromatin accessibility.<h4>Conclusions</h4>Our study identifies an IFN-γ/STAT1/CIITA axis as the central regulator of MHC-II expression in fibroblasts and reveals IL-1β as a potent suppressor of this pathway. These findings highlight a novel cytokine-mediated regulatory mechanism underlying CAF-driven immunosuppression within the tumor microenvironment."],"journal":["Cell communication and signaling : CCS"],"pubmed_title":["IL-1β-mediated suppression of CIITA attenuates IFN-γ-induced MHC-II expression on Fibroblasts."],"pmcid":["PMC12801534"],"funding_grant_id":["2022P010","82473269","32270955","BE2022719","CJ20250116","CE20235057","2024CZLJ009","YXZDXK202236","CZ20250020","CZZX202201","CZKYCMCC202301","BE2022721","NCTIB2024JS0101","2024P027"],"pubmed_authors":["Jiang J","Geng R","Fang Z","Zheng X","Chen J","Chen L","Jiang H","Wu S","Ma H","Lang Y","Tan B"],"additional_accession":[]},"is_claimable":false,"name":"IL-1β-mediated suppression of CIITA attenuates IFN-γ-induced MHC-II expression on Fibroblasts.","description":"<h4>Background</h4>Cancer-associated fibroblasts (CAFs) are key regulators in tumor microenvironment and tumor immunity, partly through MHC-II expression that modulates T-cell differentiation. However, the upstream cytokine signals controlling MHC-II expression in fibroblasts still remain poorly defined.<h4>Methods</h4>We examined MHC-II expression on fibroblasts under stimulation with interferon-γ (IFN-γ) and interleukin-1β (IL-1β) by using flow cytometry, transcriptomic analysis, and qRT-PCR. To dissect transcriptional regulation, we generated CIITA-overexpressing and CIITA-deficient fibroblast lines by lentiviral transduction and CRISPR/Cas9-mediated editing. Public scRNA-seq, ATAC-seq, and ChIP-seq datasets were further analyzed to validate molecular mechanisms.<h4>Results</h4>IFN-γ robustly up-regulated MHC-II expression on fibroblasts, while IL-1β selectively suppressed this induction without affecting PD-L1. Mechanistically, IL-1β attenuated IFN-γ-induced CIITA expression at the mRNA level but did not alter STAT1 abundance or phosphorylation. Functional assays confirmed that CIITA was indispensable for IFN-γ-driven MHC-II expression in fibroblasts. Integration of transcriptomic and epigenomic data demonstrated that CIITA directly bound MHC-II gene promoters and regulated chromatin accessibility.<h4>Conclusions</h4>Our study identifies an IFN-γ/STAT1/CIITA axis as the central regulator of MHC-II expression in fibroblasts and reveals IL-1β as a potent suppressor of this pathway. These findings highlight a novel cytokine-mediated regulatory mechanism underlying CAF-driven immunosuppression within the tumor microenvironment.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-01T03:13:03.434Z","creation":"2026-06-01T03:07:50.356Z"},"accession":"S-EPMC12801534","cross_references":{"pubmed":["41366425"],"doi":["10.1186/s12964-025-02575-4"]}}