T-bet and eomesodermin play critical roles in directing T cell differentiation to Th1 versus Th17

Y Yang, J Xu, Y Niu, JS Bromberg… - The Journal of …, 2008 - journals.aai.org
Y Yang, J Xu, Y Niu, JS Bromberg, Y Ding
The Journal of Immunology, 2008journals.aai.org
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-γ and Th1 development.
However, without T-bet, IFN-γ production and Th1 differentiation are susceptible to inhibition …
Abstract
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-γ and Th1 development. However, without T-bet, IFN-γ production and Th1 differentiation are susceptible to inhibition by IL-6 and TGFβ. As a result, Th17 development is strongly favored, the threshold for TGFβ 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 TGFβ-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.
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