TY - JOUR
T1 - IL-2-inducible T cell kinase tunes T regulatory cell development and is required for suppressive function
AU - Huang, Weishan
AU - Jeong, Ah Reum
AU - Kannan, Arun K.
AU - Huang, Lu
AU - August, Avery
N1 - Publisher Copyright:
© 2014 by The American Association of Immunologists, Inc.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1400968
DO - 10.4049/jimmunol.1400968
M3 - Article
C2 - 25063868
AN - SCOPUS:84907033007
SN - 0022-1767
VL - 193
SP - 2267
EP - 2272
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -