| First Author | Rashidi M | Year | 2018 |
| Journal | Cell Death Differ | Volume | 25 |
| Issue | 2 | Pages | 392-405 |
| PubMed ID | 29244050 | Mgi Jnum | J:274081 |
| Mgi Id | MGI:6287182 | Doi | 10.1038/cdd.2017.173 |
| Citation | Rashidi M, et al. (2018) CD52 inhibits Toll-like receptor activation of NF-kappaB and triggers apoptosis to suppress inflammation. Cell Death Differ 25(2):392-405 |
| abstractText | Soluble CD52 is a small glycoprotein that suppresses T-cell activation, but its effect on innate immune cell function is unknown. Here we demonstrate that soluble CD52 inhibits Toll-like receptor and tumor necrosis factor receptor signaling to limit activation of NF-kappaB and thereby suppress the production of inflammatory cytokines by macrophages, monocytes and dendritic cells. At higher concentrations, soluble CD52 depletes the short-lived pro-survival protein MCL-1, contributing to activation of the BH3-only proteins BAX and BAK to cause intrinsic apoptotic cell death. In vivo, administration of soluble CD52 suppresses lipopolysaccharide (LPS)-induced cytokine secretion and other features of endotoxic shock, whereas genetic deletion of CD52 exacerbates LPS responses. Thus, soluble CD52 exhibits broad immune suppressive effects that signify its potential as an immunotherapeutic agent. |
