IFN- γ and TNF- α drive a CXCL10 + CCL2 + macrophage phenotype expanded in severe COVID-19 and other diseases with tissue inflammation.

BioRxiv : the Preprint Server for Biology
Fan ZhangSoumya Raychaudhuri

Abstract

Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 and other inflammatory diseases with established therapies may help nominate immunomodulatory therapies. Using an integrative strategy, we built a reference by meta-analyzing > 300,000 immune cells from COVID-19 and 5 inflammatory diseases including rheumatoid arthritis (RA), Crohn's disease (CD), ulcerative colitis (UC), lupus, and interstitial lung disease. Our cross-disease analysis revealed that an FCN1 + inflammatory macrophage state is common to COVID-19 bronchoalveolar lavage samples, RA synovium, CD ileum, and UC colon. We also observed that a CXCL10 + CCL2 + inflammatory macrophage state is abundant in severe COVID-19, inflamed CD and RA, and expresses inflammatory genes such as GBP1, STAT1 , and IL1B . We found that the CXCL10 + CCL2 + macrophages are transcriptionally similar to blood-derived macrophages stimulated with TNF- α and IFN- γ ex vivo . Our findings suggest that IFN- γ , alongside TNF- α , might be a key driver of this abundant inflammatory macrophage phenotype in severe COVID-19 and other inflammatory diseases, which may be targeted by existing...Continue Reading

Citations

Jan 30, 2021·Current Rheumatology Reports·Aikaterini Thanou, Amr H Sawalha
Dec 29, 2020·ACS Biomaterials Science & Engineering·Bader M JaraiCatherine A Fromen

Methods Mentioned

BETA
bronchoalveolar
RNA-seq
scRNA-seq
biopsies
bronchoalveolar lavage
PCA

Clinical Trials Mentioned

NCT04337359
NCT04359290
NCT04348695

Related Concepts

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