γδ T cells and IL-17/IL-17R signaling axis in CNS inflammation

Jayasri Das Sarma
Department of Biological Sciences, Indian Institute of Science Education and Research – Kolkata, Mohanpur, Nadia, West Bengal, India

Abstract: Lymphocytes expressing γδ T-cell receptors constitute an entire system of functionally specialized subsets that have been implicated in the regulation of immune responses, including responses to pathogens and allergens, and in tissue repair. γδ T cells represent a small subpopulation of T cells that, unlike aβ T cells, function more as cells of the innate immune system. γδ T cells are known to mediate the production of inflammatory cytokines, including interferon-γ, tumor necrosis factor-a, and interleukin (IL)-17, and thus enable the activation of other subsets of infiltrating effector cells. However, not much attention was paid to γδ T cells until the recent discovery of a distinct CD4⁺ T helper (T_H) cell, T_H17 cell. CD4⁺ T cells, upon activation and expansion, develop into different T_H-cell subsets with different cytokine profiles and distinct effector functions. T cells were earlier divided into T_H1 or T_H2 cells, depending on the cytokines they produce. A third subset of IL-17-producing effector T_H cells, called T_H17 cells, has been discovered and characterized recently. Since then the literature on IL-17-producing cells has grown steadily, and several studies have focused on γδ T cells. Cytokine-mediated modulation of central nervous system (CNS) inflammatory diseases by γδ T cells in humans or in animal models is currently the subject of many studies. IL-17 and its receptor IL-17R have been implicated in the pathogenesis of immune-mediated CNS diseases, and attention has been paid to understand the mechanisms by which IL-17 cytokines and it receptor (IL-17R) family mediate the effects at a molecular level. This article reviews the studies that cover earlier aspects of γδ T cell/IL-17 biology and the new dimension of γδ T cells, IL-17, and IL-17/IL-17R signaling axis in CNS inflammation. Understanding the role of γδ T cells, IL-17, and IL-17/IL-17R signaling axis in infection and immunity could open a new avenue for immunomodulation.

Keywords: cytokine, γδ T cells, T_H17 cells, IL-17, IL-17R, multiple sclerosis, EAE, autoimmunity, CNS, viral infection, virus-induced demyelination