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ITK signalling via the Ras/IRF4 pathway regulates the development and function of Tr1 cells

Author

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  • Weishan Huang

    (Center for Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University
    Cornell University)

  • Sabrina Solouki

    (Cornell University)

  • Nicholas Koylass

    (Cornell University)

  • Song-Guo Zheng

    (Center for Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University
    Milton S. Hershey Medical Center, Pennsylvania State University)

  • Avery August

    (Cornell University)

Abstract

Type 1 regulatory T (Tr1) cells differentiate in response to signals engaging the T cell receptor (TCR), express high levels of the immunosuppressive cytokine IL-10, but not Foxp3, and can suppress inflammation and promote immune tolerance. Here we show that ITK, an important modulator of TCR signalling, is required for the TCR-induced development of Tr1 cells in various organs, and in the mucosal system during parasitic and viral infections. ITK kinase activity is required for mouse and human Tr1 cell differentiation. Tr1 cell development and suppressive function of Itk deficient cells can be restored by the expression of the transcription factor interferon regulatory factor 4 (IRF4). Downstream of ITK, Ras activity is responsible for Tr1 cell induction, as expression of constitutively active HRas rescues IRF4 expression and Tr1 cell differentiation in Itk−/− cells. We conclude that TCR/ITK signalling through the Ras/IRF4 pathway is required for functional development of Tr1 cells.

Suggested Citation

  • Weishan Huang & Sabrina Solouki & Nicholas Koylass & Song-Guo Zheng & Avery August, 2017. "ITK signalling via the Ras/IRF4 pathway regulates the development and function of Tr1 cells," Nature Communications, Nature, vol. 8(1), pages 1-15, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15871
    DOI: 10.1038/ncomms15871
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