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Gene expression analysis of WT and Stat1-/- CD4+ T cells pre and post transfer into Rag1-/- mice

ABSTRACT: Gene expression analysis of WT and Stat1-/- CD4+ T cells pre and post transfer into Rag1-/- mice

PROVIDER: PRJNA478772 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7458680.fastq.gz	Fastqsanger.gz
	SRR7458690.fastq.gz	Fastqsanger.gz
	SRR7458681.fastq.gz	Fastqsanger.gz
	SRR7458691.fastq.gz	Fastqsanger.gz
	SRR7458682.fastq.gz	Fastqsanger.gz

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Gene expression analysis of WT and Stat1-/- CD4+ T cells pre and post transfer into Rag1-/- mice

Project description:To understand the basis behind the defective survival/expansion of Stat1-/- CD4+ T cells in Rag1-/- mice, we analyzed the gene expression of WT and Stat1-/- CD4+ T cells pre- and post-transfer into these mice by RNAseq.

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Project description: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.

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