title: IL-2-inducible T cell kinase tunes T regulatory cell development and is required for suppressive function.
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.
authors: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853;
authors: Weishan
authors: http://orcid.org/0000-0002-1330-1131
authors: W
authors: Huang
authors: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853; Keck School of Medicine, University of Southern California, Los Angeles, CA 90089; and.
authors: Ah-Reum
authors: AR
authors: Jeong
authors: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853;
authors: Arun K
authors: AK
authors: Kannan
authors: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853; Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853.
authors: Lu
authors: L
authors: Huang
authors: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853; averyaugust@cornell.edu.
authors: Avery
authors: http://orcid.org/0000-0003-4968-3415
authors: A
authors: August
mesh_terms: D000818:Animals; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D018345:Mice, Knockout; D039942:Neuropilin-1 / Q000235:genetics / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D000949:Histocompatibility Antigens Class II; D039942:Neuropilin-1; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase