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.

doi:10.1101/2020.11.05.368647

bioRxiv · 10.1101/2020.11.05.368647

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.

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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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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. SLAMF7 engagement super-activates macrophages in acute and chronic inflammation. https://doi.org/10.1101/2020.11.05.368647

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