Tripartite motif-containing (TRIM) 21 negatively regulates intestinal mucosal inflammation through inhibiting TH1/TH17 cell differentiation in patients with inflammatory bowel diseases

Guangxi Zhou, Wei Wu, Lin Yu, Tianming Yu, Wenjing Yang, Ping Wang, Xiaoping Zhang, Yingzi Cong, Zhanju Liu

    Research output: Contribution to journalArticle

    8 Scopus citations

    Abstract

    Background: Tripartite motif-containing (TRIM) 21 has been implicated in the pathogenesis of several types of autoimmune diseases. Objective: We sought to elucidate TRIM21 expression in patients with inflammatory bowel diseases (IBDs) and its role in regulating intestinal mucosal inflammation. Methods: TRIM21 expression was analyzed in the inflamed mucosa of patients with IBDs by means of quantitative RT-PCR and immunohistochemistry. Peripheral blood CD4+ T cells were transfected with lentivirus-expressing TRIM21 (LV-TRIM21) or LV-sh-TRIM21, and cytokine expression was determined by using quantitative RT-PCR and ELISA. TRIM21−/− mice were generated, and trinitrobenzene sulfonic acid– and CD45RBhighCD4+ T cell–induced colitis models were established to determine its role in induction of intestinal inflammation. Results: TRIM21 was expressed predominantly in CD4+ T cells and decreased markedly in the inflamed mucosa of patients with IBDs compared with healthy control subjects. Ectopic expression of TRIM21 inhibited IBD CD4+ T cells to differentiate into TH1 and TH17 cells, whereas downregulation of TRIM21 had the opposite effects. TRIM21−/− mice had more severe colitis after administration of trinitrobenzene sulfonic acid compared with wild-type mice, which was characterized by increased expression of IFN-γ, TNF-α, and IL-17A in the colon. TRIM21−/−CD45RBhighCD4+ T cells reconstituted into recombination-activating gene (Rag1)−/− mice induced more severe colitis than in wild-type control mice. Mechanistically, interferon regulatory factor 3 was identified as a functional downstream target of TRIM21 in that silencing of interferon regulatory factor 3 suppressed TRIM21−/−CD4+ T-cell differentiation into TH1 and TH17 cells. Conclusions: TRIM21 plays a protective role in mucosal inflammation through inhibiting TH1 and TH17 cell differentiation. Thus TRIM21 might serve as a potential therapeutic target for the treatment of IBDs.

    Original languageEnglish (US)
    JournalJournal of Allergy and Clinical Immunology
    DOIs
    StateAccepted/In press - Jan 1 2018

    Keywords

    • CD4 T cells
    • inflammatory bowel disease
    • mucosal inflammation
    • T1
    • T17
    • Tripartite motif-containing 21

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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