@article{118622b0c40f41fba475a8ab397e8837,
title = "IRF4 Modulates CD8+ T Cell Sensitivity to IL-2 Family Cytokines",
abstract = "IFN regulatory factor 4 (IRF4) is a key transcription factor that promotes effector CD8+ T cell differentiation and expansion. The roles of IRF4 in regulating the CD8+ T cell response to cytokines have not been explored. In this article, we show that IL-2 and IL-15 signaling and STAT5 activation regulate IRF4 expression in CD8+ T cells. Gene-expression profile analysis has also revealed that IRF4 is required for expression of the receptors of IL-2 family cytokines CD122 and CD127. We found that IRF4 binds directly to CD122 and CD127 gene loci, indicating that it may directly promote CD122 and CD127 gene transcription. As a consequence, IRF4-deficient CD8+ T cells show diminished sensitivity to IL-2, IL-15, and IL-7 treatment in vitro. Furthermore, we found that IRF4-deficient CD8+ T cells had lower expression of CD122 and CD127 in vivo during influenza virus infection. These data suggest that IRF4 regulates the sensitivity of CD8+ T cells to IL-2 family cytokines, which correlates with the diminished effector and memory CD8+ T cell responses in IRF4-deficient CD8+ T cells.",
author = "Su Huang and Yingjia Shen and Duy Pham and Li Jiang and Zheng Wang and Kaplan, {Mark H.} and Guangjun Zhang and Jie Sun",
note = "Funding Information: Received for publication May 31, 2017. Accepted for publication July 25, 2017. Address correspondence and reprint requests to: Dr. Jie Sun, Mayo Clinic College of Medicine, 200 1st Street SW, Stabile 8-26, Rochester, MN 55905. E-mail address: Sun.Jie@mayo.edu ORCID: 0000-0002-2923-8245 (M.H.K.). The RNA sequencing data presented in this article have been submitted to the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE101510. This work was supported by National Institutes of Health Grants AI112844, AG047156, and AI076458 (to J.S.) and R01 AI095282 and AI057459 (to M.H.K.). Abbreviations used in this article: BMDC, bone marrow–derived dendritic cell; ChIP, chromatin immunoprecipitation; DC, dendritic cell; ICS, intracellular staining; IRF4, IFN regulatory factor 4; KEGG, Kyoto Encyclopedia of Genes and Genomes; MLN, mediastinal lymph node; RNA-seq, RNA sequencing; STAT5-CA, constitutive active STAT5; WT, wild-type. This article is distributed under the terms of the CC BY 4.0 Unported license. Copyright {\textcopyright} 2017 The Authors Publisher Copyright: Copyright {\textcopyright} 2017 The Authors",
year = "2017",
month = aug,
day = "1",
doi = "10.4049/immunohorizons.1700020",
language = "English (US)",
volume = "1",
pages = "92--100",
journal = "ImmunoHorizons",
issn = "2573-7732",
publisher = "NLM (Medline)",
number = "6",
}