Transcriptomics

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Gene expression profile for naïve CD4+ T cells after 60-hour-treatment by IL-27


ABSTRACT: The inhibitory receptor Tim-3 has emerged as a critical regulator of the T cell dysfunction that develops in chronic viral infections and cancers. However, little is known regarding the signaling pathways that drive Tim-3 expression. Here, we demonstrate that IL-27 induces NFIL3, which promotes permissive chromatin remodeling of the Tim-3 locus and induces Tim-3 expression together with the immunosuppressive cytokine IL-10. We further show that the IL-27/NFIL3 signaling axis is crucial for the induction of Tim-3 in vivo. IL-27-conditioned Th1 cells exhibit reduced effector function and are poor mediators of intestinal inflammation. This inhibitory effect is NFIL3 dependent. In contrast, tumor-infiltrating lymphocytes (TILs) from IL-27R-/- mice exhibit reduced NFIL3, less Tim-3 expression and failure to develop dysfunctional phenotype, resulting in better tumor growth control. Thus, our data identify an IL-27/NFIL3 signaling axis as a key regulator of effector T cell responses via induction of Tim-3, IL-10, and T cell dysfunction. Through gene expression profile analysis, we identified a series of transcription factors that are induced by IL-27. Particularly, the induction of NFIL3 is highly relevant to Tim-3 expression. Naïve CD4+ T cells from C57BL/6 mice were stimulated with plate-bound anti-CD3 and anti-CD28 antibodies for 60 hours. The cells were subjected to gene profile analysis. A comparative transcriptome analysis between cells under neutral culture condition (Untreated) and cells treated with IL-27 (IL-27-treated) was peformed to screen transcription factors that are induced by IL-27 signaling.

ORGANISM(S): Mus musculus  

SUBMITTER: Vijay K Kuchroo   Chen Zhu 

PROVIDER: E-GEOD-63628 | ArrayExpress | 2015-01-31

SECONDARY ACCESSION(S): GSE63628PRJNA268498

REPOSITORIES: GEO, ArrayExpress

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