The advent of soluble common gamma chain rocks the T cell world: A novel therapeutic target for autoimmune diseases

Abstract

The common gamma chain (γc) is the central signaling unit for the γc cytokine receptor family. γc cytokine signaling is mainly regulated by cytokine-specific receptor alpha chain expression levels but not γc expression levels. Here we will highlight that a soluble form of γc (sγc) expression, which is generated by alternative splicing, impairs naive T cell survival and promotes inflammation in a manner of inhibiting IL-7 and IL-2 signaling, representatively. Furthermore, sγc expression is significantly enhanced upon T cell activation. sγc enhances in vitro and in vivo Th17 differentiation through dampening of IL-2 signal, and sγc-overexpressing mice are consequently more susceptible to EAE. Therefore, sγc is a novel immunoregulator that control T cell biology by regulation of γc cytokine signaling.