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Activated T Cells Secrete an Alternatively Spliced Form of Common γ-Chain that Inhibits Cytokine Signaling and Exacerbates Inflammation : Activated T Cells Secrete an Alternatively Spliced Form of Common gamma-Chain that Inhibits Cytokine Signaling and Exacerbates Inflammation

Cited 44 time in Web of Science Cited 45 time in Scopus

Hong, Changwan; Luckey, Megan A.; Ligons, Davinna L.; Waickman, Adam T.; Park, Joo-Young; Kim, Grace Y.; Keller, Hilary R.; Etzensperger, Ruth; Tai, Xuguang; Lazarevic, Vanja; Feigenbaum, Lionel; Catalfamo, Marta; Walsh, Scott T. R.; Park, Jung-Hyun

Issue Date
Cell Press
Immunity, Vol.40 No.6, pp.910-923
The common gamma-chain (gamma c) plays a central role in signaling by IL-2 and other gamma c-dependent cytokines. Here we report that activated T cells produce an alternatively spliced form of gc mRNA that results in protein expression and secretion of the gamma c extracellular domain. The soluble form of gamma c (s gamma c) is present in serum and directly binds to IL-2R beta and IL-7R alpha proteins on T cells to inhibit cytokine signaling and promote inflammation. s gamma c suppressed IL-7 signaling to impair naive T cell survival during homeostasis and exacerbated Th17-cell-mediated inflammation by inhibiting IL-2 signaling upon T cell activation. Reciprocally, the severity of Th17-cell-mediated inflammatory diseases was markedly diminished in mice lacking s gamma c. Thus, s gamma c expression is a naturally occurring immunomodulator that regulates gamma c cytokine signaling and controls T cell activation and differentiation.
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