title: Interleukin (IL)-23 suppresses IL-10 in inflammatory bowel disease.
abstract: Interleukin (IL)-10 plays an important role in immune regulation in the intestine. Immune deregulation is suggested in the pathogenesis of inflammatory bowel disease (IBD). This study aims to elucidate the role of IL-23 in the suppression of IL-10 in the IBD intestinal mucosa. Surgically removed colon specimens were obtained from 16 IBD patients. The expressions of IL-10, IL-23, and IgA in the specimens were examined at the protein and gene transcriptional levels. The gene transcription of IL-10 was assessed by chromatin immunoprecipitation assay and promoter accessibility assay. The levels of IgA and IL-10 were significantly lower, whereas the levels of IL-23 were higher, in IBD specimens than in normal controls. The levels of IgA and IL-10 were negatively correlated with the infiltration of inflammatory cells in the IBD mucosa. The production of IL-10 by lamina propria mononuclear cells was lower in the IBD group than in the control group, and these levels could be enhanced by blocking IL-23. The gene transcription of IL-10 was significantly suppressed in CD4(+) T cells of IBD mucosa; this phenomenon could be replicated in vitro by adding IL-23 in the culture of polarized Th2 cells. Overexpression of IL-23 in the intestinal mucosa suppresses the production of IL-10, which weakens the defensive barrier by reducing the production of IgA in the gut.
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China. liuzhanju88@126.com
authors.forename: Zhanju
authors.initials: Z
authors.lastname: Liu
authors.forename: Bai-Sui
authors.initials: BS
authors.lastname: Feng
authors.forename: Shao-Bo
authors.initials: SB
authors.lastname: Yang
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Jingling
authors.initials: J
authors.lastname: Su
authors.forename: Ping-Chang
authors.initials: PC
authors.lastname: Yang
mesh_terms: D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D053759:Interleukin-23 / Q000096:biosynthesis* / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: C508609:IL10 protein, human; D007070:Immunoglobulin A; D053759:Interleukin-23; D016753:Interleukin-10