TCR signaling via Tec kinase ITK and interferon regulatory factor 4 (IRF4) regulates CD8(+) T-cell differentiation Journal Article


Authors: Nayar, R.; Enos, M.; Prince, A.; Shin, H.; Hemmers, S.; Jiang, J. K.; Klein, U.; Thomas, C. J.; Berg, L. J.
Article Title: TCR signaling via Tec kinase ITK and interferon regulatory factor 4 (IRF4) regulates CD8(+) T-cell differentiation
Abstract: CD8 + T-cell development in the thymus generates a predominant population of conventional naive cells, along with minor populations of "innate" T cells that resemble memory cells. Recent studies analyzing a variety of KO or knock-in mice have indicated that impairments in the T-cell receptor (TCR) signaling pathway produce increased numbers of innate CD8 + T cells, characterized by their high expression of CD44, CD122, CXCR3, and the transcription factor, Eomesodermin (Eomes). One component of this altered development is a non-CD8 + T cell-intrinsic role for IL-4. To determine whether reduced TCR signaling within the CD8 + T cells might also contribute to this pathway, we investigated the role of the transcription factor, IFN regulatory factor 4 (IRF4). IRF4 is up-regulated following TCR stimulation in WT T cells; further, this up-regulation is impaired in T cells treated with a small-molecule inhibitor of the Tec family tyrosine kinase, IL-2 inducible T-cell kinase (ITK). In contrast to WT cells, activation of IRF4-deficient CD8 + T cells leads to rapid and robust expression of Eomes, which is further enhanced by IL-4 stimulation. In addition, inhibition of ITK together with IL-4 increases Eomeso up-regulation. These data indicate that ITK signaling promotes IRF4 up-regulation following CD8 + T-cell activation and that this signaling pathway normally suppresses Eomes expression, thereby regulating the differentiation pathway of CD8 + T cells.
Keywords: itk inhibitor; t-cell receptor signal strength; t-cell signaling
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 109
Issue: 41
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2012-10-09
Start Page: E2794
End Page: E2802
Language: English
DOI: 10.1073/pnas.1205742109
PROVIDER: scopus
PMCID: PMC3478592
PUBMED: 23011795
DOI/URL:
Notes: --- - "Export Date: 2 November 2012" - "CODEN: PNASA" - "Source: Scopus"
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  1. Saskia Hemmers
    16 Hemmers