SLAMF7 engagement superactivates macrophages in acute and chronic inflammation.
Daimon P SimmonsHung N NguyenEmma Gomez-RivasYunju JeongAnna Helena JonssonAntonia F ChenJeffrey K LangeGeorge S M DyerPhilip E BlazarBrandon E EarpJonathan S CoblynElena M MassarottiJeffrey A SparksDerrick J Toddnull nullDeepak A RaoEdy Y KimMichael B BrennerPublished in: Science immunology (2022)
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.
Keyphrases
- rheumatoid arthritis
- oxidative stress
- rna seq
- immune response
- rheumatoid arthritis patients
- adipose tissue
- poor prognosis
- single cell
- disease activity
- sars cov
- coronavirus disease
- drug induced
- social media
- physical activity
- dendritic cells
- public health
- binding protein
- liver failure
- dna methylation
- copy number
- hepatitis b virus
- machine learning
- genome wide
- systemic lupus erythematosus
- electronic health record
- high glucose
- extracorporeal membrane oxygenation
- artificial intelligence
- pluripotent stem cells