Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

Opposing Roles of STAT1 and STAT3 in IL-21 Function in CD4+ T cells


ABSTRACT: Interleukin-21 (IL-21) is a type 1 cytokine essential for immune cell differentiation and function. Although IL-21 can activate several STAT family transcription factors, previous studies focused mainly on the role of STAT3 in IL-21 signaling. Here, we investigated the role of STAT1 and show that STAT1 and STAT3 have at least partially opposing roles in IL-21 signaling in CD4+ T cells. IL-21 induced STAT1 phosphorylation, and this was augmented in Stat3-deficient CD4+ T cells. RNA-Seq analysis of CD4+ T cells from Stat1- and Stat3-deficient mice revealed that both STAT1 and STAT3 are critical for IL-21-mediated gene regulation. Expression of some genes, including Tbx21 and Ifng, was differentially regulated by STAT1 and STAT3, and interestingly, ChIP-Seq analysis showed that STAT3 binding at Tbx21 and Ifng loci was attenuated in Stat1-deficient cells. Moreover, opposing actions of STAT1 and STAT3 on IFN- expression in CD4+ T cells were demonstrated in vivo during chronic lymphocytic choriomeningitis (LCMV) infection. Finally, IL-21-mediated induction of STAT1 phosphorylation, as well as IFNG and TBX21 expression, were higher in CD4+ T cells from patients with autosomal dominant hyper-IgE syndrome (AD-HIES), which is caused by STAT3 deficiency. These data indicate an interplay between STAT1 and STAT3 in fine-tuning IL-21 actions. Genome-wide transcription factors mapping and binding of STAT3 in mouse CD4+ T cells in both WT and Stat1-deficient mice. RNA-Seq is performed in mouse CD4+ T cells in WT, Stat1-deficient and Stat3-deficient mice.

ORGANISM(S): Mus musculus

SUBMITTER: Peng Li 

PROVIDER: E-GEOD-63204 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

Similar Datasets

2015-07-07 | E-GEOD-61677 | biostudies-arrayexpress
2019-02-08 | E-MTAB-6273 | biostudies-arrayexpress
2010-01-08 | E-GEOD-19198 | biostudies-arrayexpress
2015-07-01 | GSE63204 | GEO
2017-05-03 | E-GEOD-67183 | biostudies-arrayexpress
2013-02-14 | E-GEOD-27161 | biostudies-arrayexpress
2015-05-27 | E-GEOD-65621 | biostudies-arrayexpress
2020-05-26 | PXD010612 | Pride
2010-08-31 | E-GEOD-23681 | biostudies-arrayexpress
2022-04-04 | E-MTAB-10758 | biostudies-arrayexpress