내용요약(Abstract)
The common γ-chain (γc) plays a central role in signaling by IL-2 and other γc？dependent cytokines. I will present that activated T cells produce an alternatively spliced form of γc that results in secretion of the γc extracellular domain. The soluble form of γc (sγc) was produced only by alternative splicing and not receptor shedding, and directly bound to IL-2Rβ and IL-7Rα proteins on T cells to inhibit cytokine signaling and promote inflammation. Soluble γc impaired na？ve T cell survival by suppressing IL-7 signaling during homeostasis and enhanced Th17-mediated inflammation by inhibiting IL-2 signaling upon T cell activation, as sγc-overexpressing mice are consequently more susceptible to EAE. Thus, sγc expression is a new mechanism for regulating cytokine signaling and controlling T cell activation and differentiation. Furthermore, these data may lead to the generation of novel therapeutic targets for the treatment of inflammatory autoimmune diseases, as sγc is genetically conserved in human and circulating levels of sγc have been linked to autoimmune diseases patients.