| First Author | Zhou G | Year | 2018 |
| Journal | J Allergy Clin Immunol | Volume | 142 |
| Issue | 4 | Pages | 1218-1228.e12 |
| PubMed ID | 29113905 | Mgi Jnum | J:350064 |
| Mgi Id | MGI:6823106 | Doi | 10.1016/j.jaci.2017.09.038 |
| Citation | Zhou G, et al. (2018) Tripartite motif-containing (TRIM) 21 negatively regulates intestinal mucosal inflammation through inhibiting TH1/TH17 cell differentiation in patients with inflammatory bowel diseases. J Allergy Clin Immunol 142(4):1218-1228.e12 |
| abstractText | 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 CD45RB(high)CD4(+) 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-gamma, TNF-alpha, and IL-17A in the colon. TRIM21(-/-)CD45RB(high)CD4(+) 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. |
