fzhangcode/inflamedtissue_covid19_reference

Overview

This repo provides the source code for our analysis and figures for

• Citation: Fan Zhang, Joseph R. Mears, Lorien Shakib, Jessica I. Beynor, Sara Shanaj, Ilya Korsunsky, Aparna Nathan, Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, Laura T. Donlin*, Soumya Raychaudhuri*. IFN-γ and TNF-α drive a CXCL10+ CCL2+ macrophage phenotype expanded in severe COVID-19 lungs and inflammatory diseases with tissue inflammation. In review, 2021.

• Motivation: Understanding the immune cell states shared between COVID-19 and other inflammatory diseases with established therapies may help nominate immunomodulatory therapies.

• Build an immune cell reference consisting of >300,000 single-cell transcriptomic profiles from COVID-19 affected lungs and tissues from healthy subjects and patients with 5 inflammatory diseases: rheumatoid arthritis (RA), Crohn’s disease (CD), ulcerative colitis (UC), lupus, and interstitial lung disease. We tested the association of shared immune states with severe/inflamed status compared to healthy control using mixed-effects modeling.

• Identify a CXCL10+ CCL2+ inflammatory macrophage state that is shared and strikingly abundant in severe COVID-19 bronchoalveolar lavage samples, inflamed RA synovium, inflamed CD ileum and UC colon. We found this macrophage phenotype is induced upon co-stimulation by IFN-γ and TNF-α.

• This reference can be used to query/investigate cells from other inflammatory diseases and their transcriptomic similarities with our reference which incorporates 5 inflammatory diseased tissues and COVID-19 BALF. A proof of concept of mapping Sepsis PBMCs (Reyes, et al, Nature Medicine, 2020) to our cross-diseased tissue single-cell reference that reflects shared inflammatory structures.

Data access

The single-cell RNA-seq data for blood-derived macrophages are available in the Gene Expression Omnibus database with accession number GSE168710.

Contact

Send us an email ([email protected] and [email protected]) if you have additional questions!