Tripartite motif-containing (TRIM) 21 negatively regulates intestinal mucosal inflammation through inhibiting TH1/TH17 cell differentiation in patients with inflammatory bowel diseases - 05/10/18
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.
Le texte complet de cet article est disponible en PDF.Key words : Tripartite motif-containing 21, inflammatory bowel disease, CD4+ T cells, mucosal inflammation, TH1, TH17
Abbreviations used : A-CD, A-UC, CD, CDAI, HC, IBD, IRF3, LP, LV, LV-NC, 2-ME, NF-κB, qRT-PCR, TNBS, Rag1, R-CD, RORγt, R-UC, SLE, TALEN, TRIM, UC, WT
Plan
Supported by grants from the National Natural Science Foundation of China (81770546, 81630017, and 81470822). |
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Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 142 - N° 4
P. 1218 - octobre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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