| First Author | Hong C | Year | 2014 |
| Journal | Immunity | Volume | 40 |
| Issue | 6 | Pages | 910-23 |
| PubMed ID | 24909888 | Mgi Jnum | J:257989 |
| Mgi Id | MGI:6112329 | Doi | 10.1016/j.immuni.2014.04.020 |
| Citation | Hong C, et al. (2014) Activated T cells secrete an alternatively spliced form of common gamma-chain that inhibits cytokine signaling and exacerbates inflammation. Immunity 40(6):910-23 |
| abstractText | The common gamma-chain (gammac) plays a central role in signaling by IL-2 and other gammac-dependent cytokines. Here we report that activated T cells produce an alternatively spliced form of gammac mRNA that results in protein expression and secretion of the gammac extracellular domain. The soluble form of gammac (sgammac) is present in serum and directly binds to IL-2Rbeta and IL-7Ralpha proteins on T cells to inhibit cytokine signaling and promote inflammation. sgammac 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 sgammac. Thus, sgammac expression is a naturally occurring immunomodulator that regulates gammac cytokine signaling and controls T cell activation and differentiation. |
