CD52 inhibits Toll-like receptor activation of NF-κB and triggers apoptosis to suppress inflammation

Maryam Rashidi, Esther Bandala-Sanchez, Kate E. Lawlor, Yuxia Zhang, Alana M. Neale, Swarna L. Vijayaraj, Robert O'Donoghue, John M. Wentworth, Timothy E. Adams, James E. Vince, Leonard C. Harrison

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

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-κB 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.

Original languageEnglish
Pages (from-to)392-405
Number of pages14
JournalCell Death and Differentiation
Volume25
Issue number2
DOIs
Publication statusPublished - 1 Jan 2018
Externally publishedYes

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