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Type I interferon-enhanced IL-10 expression in human CD4 T cells is regulated by STAT3, STAT2, and BATF transcription factors

Abstract : Type I IFN can exert pro- and anti-inflammatory activities in the immune system. Here, we have investigated the mechanism by which IFN-α enhances early expression of the anti-inflammatory cytokine IL-10 in human CD45RA+CD4+ T cells. With the use of transcriptomic and biochemical approaches, we found distinct and combined contributions of the IFN and the TCR signaling pathways to the induction of STAT1/2/3 and the basic leucine zipper activating transcription factor-like (BATF) family members. Moreover, IFN-induced STAT3 phosphorylation was prolonged by the TCR response, whereas IFN-induced STAT2 phosphorylation was of long duration. With the use of RNA interference (RNAi), we identified STAT3 as the major actor and STAT2 as a contributor of the IFN action on IL-10 Upon TCR/IFN costimulation, STAT3 directly bound at the IL-10 conserved noncoding sequence (CNS)- 9, an enhancer element known to recruit BATF in CD4 T cells. The cosilencing of the 3 BATFs resulted in an overall reduction of IL-10 expression, but the promoting activity of IFN-α was retained. These results support the notion that the IFN action is indexed on BATF function and provide evidence for a cooperation between BATFs and STAT3, the latter being activated via early IFN and delayed TCR effects.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02136992
Contributor : Marie-Luce Kop <>
Submitted on : Wednesday, May 22, 2019 - 3:30:41 PM
Last modification on : Thursday, May 28, 2020 - 11:16:03 AM

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Umeshree Govender, Béatrice Corre, Yasmine Bourdache, Sandra Pellegrini, Frédérique Michel. Type I interferon-enhanced IL-10 expression in human CD4 T cells is regulated by STAT3, STAT2, and BATF transcription factors. Journal of Leukocyte Biology, Society for Leukocyte Biology, 2017, 101 (5), pp.1181-1190. ⟨10.1189/jlb.2A0416-187RR⟩. ⟨pasteur-02136992⟩

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