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SLAMF7 engagement super-activates macrophages in acute and chronic inflammation

Simmons, D. P.; Nguyen, H.; Gomez-Rivas, E.; Jeong, Y.; Chen, A. F.; Lange, J. K.; Dyer, G. S.; Blazar, P.; Earp, B. E.; RA/SLE Network, A. M. P.; Rao, D. A.; Kim, E. Y.; Brenner, M. B.

2020-11-05 immunology
10.1101/2020.11.05.368647 bioRxiv
Show abstract

Macrophages regulate protective immune responses to infectious microbes, but aberrant macrophage activation frequently drives pathological inflammation. To identify regulators of vigorous macrophage activation, we analyzed RNA-seq data from synovial macrophages and identified SLAMF7 as a receptor associated with a super-activated macrophage state in rheumatoid arthritis. We implicated IFN-{gamma} as a key regulator of SLAMF7 expression. Engaging this receptor drove an exuberant wave of inflammatory cytokine expression, and induction of TNF- following SLAMF7 engagement amplified inflammation through an autocrine signaling loop. We observed SLAMF7-induced gene programs not only in macrophages from rheumatoid arthritis patients, but in gut macrophages from active Crohns disease patients and lung macrophages from severe COVID-19 patients. This suggests a central role for SLAMF7 in macrophage super-activation with broad implications in pathology.

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