IRF5 Acts As a Potential Therapeutic Marker in Inflammatory Bowel Disease

Abstract

Background: Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronically inflammatory disorders. Interferon regulatory factor (IRF) 5 is reported to be involved in the pathogenesis of several inflammatory diseases. However, the exact role of IRF5 in IBD is still obscure. Materials and Methods: IRF5 expression was analyzed in peripheral blood mononuclear cells (PBMCs) and inflamed mucosa of patients with IBD by means of qRT-PCR and immunohistochemistry. Peripheral blood CD4+ T cells were stimulated with inflammatory cytokines, and transfected with lentivirus-expressing IRF5 (LV-IRF5) or LV-sh-IRF5, and then cytokine expression was determined by using Flow cytometry, qRT-PCR and ELISA. Results: IRF5 was significantly increased in PBMCs and inflamed mucosa in patients with active IBD, and was significantly correlated with disease activity. Upregulation of IRF5 not only could promote IBD CD4+ T cells to differentiate into Th1 and Th17 cells through modulation of T-bet and RORC, but also suppressed IL-10 expression via targeting its promoter sites directly, whereas downregulation of IRF5 had the opposite effects. TNF-α upregulated IRF5 expression in CD4+ T cells, and anti-TNF treatment with infliximab (IFX) could significantly decrease IRF5 expression in CD4+ T cells and intestinal mucosa in patients with CD. Conclusions: Our study reveal a novel mechanism in which elevated IRF5 levels in IBD were correlated with disease activity, and might serve as a potential therapeutic marker for the treatment of IBD via promoting Th1/17 cell immune responses and inhibiting IL-10 expression. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (81800501), the Natural Science Foundation of Shandong Province, China (ZR2018BH004), the key Research and Development Plan of Shandong Province (2018GSF118214), and the PhD Research Startup Foundation of the Affiliated Hospital of Jining Medical University (2017-BS-004). Declaration of Interests: The authors do not have any conflicts of interest. Ethics Approval Statement: This study was approved by the Institutional Review Board for Clinical Research of the Affiliated Hospital of Jining Medical University and the Shanghai Tenth People’s Hospital of Tongji University. Written informed consent was also obtained from all subjects before study.