MIR-301a promotes intestinal mucosal inflammation through induction of IL-17A and TNF-α in IBD

Chong He, Yan Shi, Ruijin Wu, Mingming Sun, Leilei Fang, Wei Wu, Changqin Liu, Maochun Tang, Zhong Li, Ping Wang, Yingzi Cong, Zhanju Liu

    Research output: Contribution to journalArticlepeer-review

    58 Scopus citations

    Abstract

    Objective: MicroRNA (miR)-301a is known to be involved in the tumourigenesis and pathogenesis of several autoimmune diseases, but it remains unclear whether miR-301a is associated with the pathogenesis of IBD. Methods: miR-301a expression was assessed in peripheral blood mononuclear cells (PBMC) and inflamed mucosa of patients with IBD by quantitative real-time-PCR. Peripheral blood CD4+ T cells were transduced with lentivirus-encoding pre-miR-301a (LV-miR-301a) or a reverse complementary sequence of miR-301a (LV-anti-miR-301a), and their differentiation and activation were investigated in vitro. Antisense miR-301a was administered into mice during trinitrobenzene sulphonic acid (TNBS)-induced colitis to determine its role in colitis. Results: miR-301a expression was significantly upregulated in PBMC and inflamed mucosa of patients with IBD compared with healthy controls. Stimulation with tumour necrosis factor-α (TNF-α) significantly enhanced miR-301a expression in IBD CD4+ T cells, which was markedly reversed by anti-TNF-α mAb (Infliximab) treatment. Transduction of LV-miR-301a into CD4+ T cells from patients with IBD promoted the Th17 cell differentiation and TNF-α production compared with the cells with expression of LV-anti-miR-301a. SNIP1 as a functional target of miR-301a was reduced in miR-301a expression but increased in LV-anti-miR-301a expression. Knockdown of SNIP1 could enhance Th17 cell differentiation. Furthermore, intracolonical administration of antisense miR-301a in TNBS-induced mouse colitis model significantly decreased numbers of interleukin (IL)-17A+ cells and amounts of pro-inflammatory cytokines (eg, IL-17A, TNF-α) in inflamed colon. Conclusions: Our data reveal a novel mechanism in which the elevated miR-301a in PBMC and inflamed mucosa of IBD promotes Th17 cell differentiation through downregulation of SNIP1. Blockade of miR-301a in vivo may serve as a novel therapeutic approach in the treatment of IBD.

    Original languageEnglish (US)
    Pages (from-to)1938-1950
    Number of pages13
    JournalGut
    Volume65
    Issue number12
    DOIs
    StatePublished - Dec 1 2016

    Keywords

    • IBD BASIC RESEARCH
    • IMMUNOREGULATION
    • MUCOSAL IMMUNITY

    ASJC Scopus subject areas

    • Gastroenterology

    Fingerprint Dive into the research topics of 'MIR-301a promotes intestinal mucosal inflammation through induction of IL-17A and TNF-α in IBD'. Together they form a unique fingerprint.

    Cite this