SLAMF7 engagement superactivates macrophages in acute and chronic inflammation.
Sci Immunol
; 7(68): eabf2846, 2022 02 11.
Article
in English
| MEDLINE | ID: covidwho-1685480
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 superactivated macrophage state in rheumatoid arthritis. We implicated IFN-γ as a key regulator of SLAMF7 expression and engaging SLAMF7 drove a strong wave of inflammatory cytokine expression. Induction of TNF-α after SLAMF7 engagement amplified inflammation through an autocrine signaling loop. We observed SLAMF7-induced gene programs not only in macrophages from rheumatoid arthritis patients but also in gut macrophages from patients with active Crohn's disease and in lung macrophages from patients with severe COVID-19. This suggests a central role for SLAMF7 in macrophage superactivation with broad implications in human disease pathology.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Transcriptome
/
Signaling Lymphocytic Activation Molecule Family
/
Inflammation
/
Macrophage Activation
Limits:
Adult
/
Female
/
Humans
Language:
English
Journal:
Sci Immunol
Year:
2022
Document Type:
Article
Affiliation country:
Sciimmunol.abf2846
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