| First Author | Liao G | Year | 2012 |
| Journal | Gastroenterology | Volume | 142 |
| Issue | 3 | Pages | 582-591.e8 |
| PubMed ID | 22155173 | Mgi Jnum | J:315218 |
| Mgi Id | MGI:6829820 | Doi | 10.1053/j.gastro.2011.11.031 |
| Citation | Liao G, et al. (2012) Glucocorticoid-induced tumor necrosis factor receptor family-related protein regulates CD4(+)T cell-mediated colitis in mice. Gastroenterology 142(3):582-591.e8 |
| abstractText | BACKGROUND & AIMS: The glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR; also called TNFRSF18 or CD357) regulates the T cell-mediated immune response and is present on surfaces of regulatory T (Treg) cells and activated CD4(+) T cells. We investigated the roles of GITR in the development of colitis in mice. METHODS: Chronic enterocolitis was induced by the transfer of wild-type or GITR(-/-) CD4(+) T cells to GITR(-/-) x Rag(-/-) or Rag(-/-) mice. We determined the severity of colitis by using the disease activity index; measured levels of inflammatory cytokines, T cells, and dendritic cells; and performed histologic analysis of colon samples. RESULTS: Transfer of nonfractionated CD4(+) cells from wild-type or GITR(-/-) donors induced colitis in GITR(-/-) x Rag(-/-) but not in Rag(-/-) mice. Among mice with transfer-induced colitis, the percentage of Treg and T-helper (Th) 17 cells was reduced but that of Th1 cells increased. Treg cells failed to prevent colitis in GITR(-/-) x Rag(-/-) recipients; this was not the result of aberrant function of GITR(-/-) Treg or T effector cells but resulted from an imbalance between the numbers of tolerogenic CD103(+) and PDCA1(+) plasmacytoid dendritic cells in GITR(-/-) mice. This imbalance impaired Treg cell development and expanded the Th1 population in GITR(-/-) x Rag(-/-) mice following transfer of nonfractionated CD4(+) cells. CONCLUSIONS: GITR is not required on the surface of Treg and T effector cells to induce colitis in mice; interactions between GITR and its ligand are not required for induction of colitis. GITR instead appears to control dendritic cell and monocyte development; in its absence, mice develop aggravated chronic enterocolitis via an imbalance of colitogenic Th1 cells and Treg cells. |
