| First Author | Yang Y | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 12 | Pages | 8700-10 |
| PubMed ID | 19050290 | Mgi Jnum | J:142051 |
| Mgi Id | MGI:3820339 | Doi | 10.4049/jimmunol.181.12.8700 |
| Citation | Yang Y, et al. (2008) T-bet and Eomesodermin play critical roles in directing T cell differentiation to Th1 versus Th17. J Immunol 181(12):8700-10 |
| abstractText | Th1 and Th17 cells are crucial in immune regulation and autoimmune disease development. By adding Stat6 deficiency to T-bet deficiency, and thus negating effects from elevated levels of IL-4/Stat6/GATA3 Th2 signals in T-bet-deficient cells, we investigated the signals important for Th1 and Th17 cell differentiation and their role in colitis development. The data reveal that Eomesodermin compensates T-bet deficiency for IFN-gamma and Th1 development. However, without T-bet, IFN-gamma production and Th1 differentiation are susceptible to inhibition by IL-6 and TGFbeta. As a result, Th17 development is strongly favored, the threshold for TGFbeta requirement is lowered, and IL-6 drives Th17 differentiation, elucidating a critical role for T-bet in directing T cell differentiation to Th1 vs Th17. In contrast to IL-6 plus TGFbeta-driven Th17, IL-6-driven Th17 cells do not express IL-10 and they induce a more intense colitis. Naive CD4 T cells deficient in Stat6 and T-bet also induce a Th17-dominant colitis development in vivo. Our data provide new insights into the choice between Th1 and Th17 development and their roles in autoimmunity. |
