IL-2-inducible T cell kinase tunes T regulatory cell development and is required for suppressive function

Weishan Huang, Ah Reum Jeong, Arun K. Kannan, Lu Huang, Avery August

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

IL-2-inducible T cell kinase (ITK) is a key signaling mediator downstream of TCR, mediating T cell positive selection, as well as innate T cell and CD4+Th2/Th17 differentiation. In this article, we show that ITK also negatively tunes IL-2-induced expansion of conventional Foxp3-expressing regulatory T cells (Tregs). In vivo, Treg abundance is inversely correlated with ITK expression, and inducible Treg development is inversely dependent on ITK kinase activity. While Treg development normally requires both hematopoietic and thymic MHC class 2 (MHC2) expression, the absence of ITK allows Treg development with MHC2 expression in either compartment, with preference for selection by thymic MHC2, suggesting a gatekeeper role for ITK in ensuring that only Tregs selected by both thymic and hematopoietic MHC2 survive selection. Although ITK suppresses Treg development and is not required for maintenance of neuropilin-1-positive natural Tregs in the periphery, it is indispensable for Treg functional suppression of naive CD4+T cell-induced colitis in Rag-/-recipients. ITK thus regulates the development and function of Tregs. Copyright

Original languageEnglish (US)
Pages (from-to)2267-2272
Number of pages6
JournalJournal of Immunology
Volume193
Issue number5
DOIs
StatePublished - Sep 1 2014

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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