Viral RNA–unprimed Rig-I restrains Stat3 activation in the modulation of regulatory T Cell/Th17 cell balance

H Yang, HZ Guo, XY Li, J Lin, W Zhang… - The Journal of …, 2017 - journals.aai.org
H Yang, HZ Guo, XY Li, J Lin, W Zhang, JM Zhao, HX Zhang, SJ Chen, Z Chen, J Zhu
The Journal of Immunology, 2017journals.aai.org
Innate immunity activation by viral RNA–primed retinoid acid inducible gene-I (Rig-I) in
CD4+ T cells antagonizes TGFβ signaling to suppress the differentiation of regulatory T cells
(Tregs). However, how viral RNA–unliganded Rig-I (apo–Rig-I) modulates Treg generation
remains unclear. In this article, we show that, in the absence of viral infection, Treg
differentiation of Rig-I−/− CD4+ T cells was compromised, in the presence of increased
generation of Th17 cells and overactivation of Stat3, a critical regulator tilting the Treg/Th17 …
Abstract
Innate immunity activation by viral RNA–primed retinoid acid inducible gene-I (Rig-I) in CD4+ T cells antagonizes TGFβ signaling to suppress the differentiation of regulatory T cells (Tregs). However, how viral RNA–unliganded Rig-I (apo–Rig-I) modulates Treg generation remains unclear. In this article, we show that, in the absence of viral infection, Treg differentiation of Rig-I−/− CD4+ T cells was compromised, in the presence of increased generation of Th17 cells and overactivation of Stat3, a critical regulator tilting the Treg/Th17 cell balance. Mechanistically, apo–Rig-I physically associates with Stat3, thereby inhibiting Jak1’s association with Stat3 while facilitating Shp2’s association to inhibit p-Stat3 levels. Interestingly, inhibition of Stat3 ameliorates the Treg/Th17 imbalance and the colitis observed in Rig-I−/− mice. Collectively, these results uncover an independent functional contribution of the apo–Rig-I/Stat3 interaction in the maintenance of Treg/Th17 cell balance.
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