title: Interleukin 35 Rescues Regulatory B Cell Function, but the Effect Is Dysregulated in Ulcerative Colitis.
abstract: Ulcerative colitis (UC) is a long-time inflammatory condition arising from aberrant immune activation in the colon and the rectum. Interleukin (IL)-35 plays critical roles in autoimmune disorders. In this study, we explored the pathways of IL-35 in affecting UC. First, peripheral blood mononuclear cells (PBMCs) from UC patients were obtained. Pretreating PBMCs with IL-35 resulted in significantly elevated IL-10 production from whole PBMCs as well as B cells, whereas pretreating PBMCs with IL-12 or IL-27 did not demonstrate a similar effect. IL-35 suppressed the proliferation of CD4+CD25-conventional T cells, CD4+CD25+regulatory T (Treg) cells, and CD8+T cells, but did not inhibit the proliferation of B cells. IL-35-mediated IL-10 secretion in B cells did not require the presence of Treg cells. After treatment with IL-35, B cells from UC patients presented significantly enhanced regulatory function, characterized by inhibiting cell proliferation and interferon (IFN)-γ, IL-17, and tumor necrosis factor (TNF)-α secretion from autologous CD4+CD25-T cells and CD8+T cells, which was dependent on IL-10 signaling. However, IL-35-treatment did not demonstrate an effect on regulating IL-5 and IL-13 responses. These discoveries identified a Th1, Th17, and CD8+T cell-targeting role of IL-35 in UC patients. Next, we examined the IL-35 expression in the intestinal mucosal in UC patients. Data showed that both noninflamed and inflamed tissues from UC patients presented significantly lower IL-35 secretion compared to healthy control tissues, which was associated with suppressed p35 transcription. UC patients with higher IL-35 also presented higher IL-10 secretion in gut mucosa. Together, our study identified that IL-35 could mediate anti-inflammatory function through promoting regulatory B cell functions, but this effect was suppressed in UC patients.
authors.affiliation: 1 Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University , Jinan, China .|2 Department of Gastroenterology, The First People's Hospital of Jining , Jining, China .
authors.forename: Shaoxuan
authors.initials: S
authors.lastname: Wang
authors.affiliation: 1 Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University , Jinan, China .
authors.forename: Chengyong
authors.initials: C
authors.lastname: Qin
mesh_terms: D000368:Aged; D060151:B-Lymphocytes, Regulatory / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007378:Interleukins / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D008875:Middle Aged
chemical_list: C508609:IL10 protein, human; D007378:Interleukins; C532417:interleukin-35, human; D016753:Interleukin-10
keywords: B cell; interleukin 35; ulcerative colitis