CD52 inhibits Toll-like receptor activation of NF-kappaB and triggers apoptosis to suppress inflammation
- Author(s)
- Rashidi, M; Bandala-Sanchez, E; Lawlor, KE; Zhang, Y; Neale, AM; Vijayaraj, SL; O'Donoghue, R; Wentworth, JM; Adams, TE; Vince, JE; Harrison, LC;
- Details
- Publication Year 2018-02,Volume 25,Issue #2,Page 392-405
- Journal Title
- Cell Death and Differentiation
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- Springer Nature
- Research Division(s)
- Inflammation; Population Health And Immunity
- PubMed ID
- 29244050
- Publisher's Version
- https://doi.org/10.1038/cdd.2017.173
- NHMRC Grants
- NHMRC/1037321, NHMRC/1051484, NHMRC/1051210, NHMRC/1101405, NHMRC/1080887, NHMRC/1052598,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2018-01-15 12:39:51
Last Modified: 2018-06-27 09:15:08