title: The signaling axis of microRNA-31/interleukin-25 regulates Th1/Th17-mediated inflammation response in colitis.
abstract: Interleukin-25 (IL-25) is an important regulatory cytokine that has a key role on mucosal immune tolerance during inflammation response. However, the molecular mechanism that regulates the colonic IL-25 expression in Crohn's disease (CD) remains unclear. In this study, IL-25 level was proved to decrease in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis mice and IL-10 knockout (KO) spontaneous colitis mice. An inverse correlation between IL-25 and miR-31 was discovered in the colons from model mice and CD patients. Furthermore, target validation analysis demonstrated that miR-31 directly regulated IL-25 expression by binding to its messenger RNA 3'-untranslated region. Changing colonic miR-31 level in the colitis mice could affect the mucosal IL-12/23-mediated Th1/Th17 pathway and lead to either amelioration or aggravation of colonic inflammation. In addition, the therapeutic effects of anti-miR-31 in TNBS-induced colitis were abolished by colonic treatment with IL-25 antibody or colonic down-expression of IL-25. Our findings demonstrated that IL-25 could be a crucial anti-inflammatory cytokine in TNBS-induced colitis and the signaling of miR-31 targeting IL-25 might be a possible mechanism that regulates IL-12/23-mediated Th1/Th17 inflammatory responses during colonic inflammation process. Restoring colonic IL-25 expression and blocking Th1/Th17 responses via intracolonic administration of miR-31 inhibitor may represent a promising approach for CD treatment.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: T
authors.initials: T
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.|State Key Laboratory of Analytical Chemistry for Life Sciences and Collaborative Innovation Center of Chemistry for Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.|State Key Laboratory of Analytical Chemistry for Life Sciences and Collaborative Innovation Center of Chemistry for Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics; D020381:Interleukin-17 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015398:Signal Transduction / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014302:Trinitrobenzenesulfonic Acid; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D019138:Antibodies, Blocking; C486701:IL25 protein, human; D020381:Interleukin-17; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D016753:Interleukin-10; D014302:Trinitrobenzenesulfonic Acid