Deltex-1 is indispensible for the IL-6 and TGF-β treatment-triggered differentiation of Th17 cells.

Published on Jul 22, 2020in Cellular Immunology4.078
· DOI :10.1016/J.CELLIMM.2020.104176
Zhengle Tang2
Estimated H-index: 2
(JNU: Jinan University),
Yuan Wang2
Estimated H-index: 2
(JNU: Jinan University)
+ 3 AuthorsFeiyue Xing12
Estimated H-index: 12
(JNU: Jinan University)
Sources
Abstract
Abstract CSL(CBF1, Su(H) and LAG-1)-dependent Hes-1 signaling plays an important part in regulating Th17 cell differentiation. However, little is known about influence of CSL-independent Deltex-1 signaling on this subset. The current focus is on roles of the Deltex-1 signaling in the Th17 cell differentiation. IL-17-producing CD4+ T cell subpopulation could be induced in vitro by treatment of both IL-6 and TGF-β. This could be reversed by knockdown of the deltex-1 gene, following the attenuation of retinoic acid-related orphan receptor γt (RORγt) and its DNA-binding activity in nuclei. Subsequently, Th17-associated cytokines generated by the treated cells were also diminished by the inhibition of Deltex-1 signaling, but the production of IL-10 was enhanced. Contrary to the alteration of RORγt, both zinc-finger transcription factor-3 (GATA3) and transcription factor Forkhead box P3 (Foxp3) were augmented at their mRNA and protein levels as well as DNA-binding activities with the emerging phenotypes of the corresponding cellular subpopulation and T-bet (encoded by TBX21) was not changed. These results reveal for the first time that Deltex-1 is indispensible for the IL-6 and TGF-β treatment-triggered differentiation of Th17 cells, indicating that CSL-independent Deltex-1 signaling favors naive CD4+ T cells to deviate into Th17 cells via the enhancement of RORγt/IL-17A.
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