Diversity of IL-17-producing T lymphocytes
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Cellular and Molecular Life Sciences
REVIEW
Diversity of IL-17-producing T lymphocytes Jiyeon S. Kim • Martha S. Jordan
Received: 2 May 2012 / Revised: 31 July 2012 / Accepted: 6 September 2012 Ó Springer Basel AG 2012
Abstract Interleukin (IL)-17 is a pro-inflammatory cytokine that plays critical roles in host defense against extracellular bacteria and fungi and also in the pathogenesis of autoimmune diseases. While CD4? TCRab? T helper (Th) 17 cells are the best-described cellular source of IL-17, many innate-like T cells are in fact potent producers of IL-17. Given the increasing interest in therapeutic modulation of the IL-17 axis, it is crucial to better understand the cellular origins of IL-17 in various infection and diseases settings. While the diverse population of IL-17producing T cells share many common characteristics, notable differences also exist. In this review, we discuss the heterogeneity of IL-17-producing T cell types focusing on their development, regulation, and function. Keywords Cytokine Th17 cells nTh17 cells cd T cells iNKT cells Host defense Autoimmunity
Introduction CD4? TCRab? T helper (Th) cells play a central role in orchestrating immune response by producing a distinct array of cytokines depending on each subset. The Th1/Th2 paradigm of CD4? T cell differentiation, first proposed by
J. S. Kim Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA M. S. Jordan (&) Department of Pathology and Laboratory Medicine, University of Pennsylvania, 414 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104, USA e-mail: [email protected]
Mosmann and Coffman 25 years ago [1], helped clarify many phenomena of the adaptive immune system, albeit with some unexplained enigmas. While an imbalance in Th1 cell function was thought to result in autoimmunity, subsequent studies demonstrated that mice lacking interferon (IFN)-c, a Th1 cytokine, as well as mice deficient of molecules required for Th1 cell differentiation developed more severe experimental autoimmune encephalomyelitis (EAE) [2–4], a mouse model of multiple sclerosis (MS). This paradox was solved when interleukin (IL)-23 was found to be crucial for the induction of EAE [5] and by the following discovery that IL-23 expands a population of IL17-producing CD4? T cells that are capable of inducing EAE [6]. Closely following this observation, multiple studies established this novel population as a distinct T helper cell subset, Th17 cells, and the immunology community welcomed a new and important member to the CD4? T cell family. Discovery of Th17 cells generated new interest and excitement for the cytokine IL-17. Murine IL-17 was first identified in 1993 [7] (human IL-17 was cloned in 1996 [8]) but had remained underexplored. IL-17 is a proinflammatory cytokine that induces production of other pro-inflammatory cytokines and chemokines from target cells; the IL-17 receptor is ubiquitously expressed on hematopoietic and non-hematopoietic cells through
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