| First Author | Chen CW | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 6 | Pages | 1961-1966 |
| PubMed ID | 28768726 | Mgi Jnum | J:251011 |
| Mgi Id | MGI:6103524 | Doi | 10.4049/jimmunol.1700375 |
| Citation | Chen CW, et al. (2017) Cutting Edge: 2B4-Mediated Coinhibition of CD4(+) T Cells Underlies Mortality in Experimental Sepsis. J Immunol 199(6):1961-1966 |
| abstractText | Sepsis is a leading cause of death in the United States, but the mechanisms underlying sepsis-induced immune dysregulation remain poorly understood. 2B4 (CD244, SLAM4) is a cosignaling molecule expressed predominantly on NK cells and memory CD8(+) T cells that has been shown to regulate T cell function in models of viral infection and autoimmunity. In this article, we show that 2B4 signaling mediates sepsis lymphocyte dysfunction and mortality. 2B4 expression is increased on CD4(+) T cells in septic animals and human patients at early time points. Importantly, genetic loss or pharmacologic inhibition of 2B4 significantly increased survival in a murine cecal ligation and puncture model. Further, CD4-specific conditional knockouts showed that 2B4 functions on CD4(+) T cell populations in a cell-intrinsic manner and modulates adaptive and innate immune responses during sepsis. Our results illuminate a novel role for 2B4 coinhibitory signaling on CD4(+) T cells in mediating immune dysregulation. |
