High-throughput analysis of lung immune cells in a combined murine model of agriculture dust-triggered airway inflammation with rheumatoid arthritis

• Published in: PloS one Vol. 16; no. 2; p. e0240707
• Main Authors: Gaurav, Rohit, Mikuls, Ted R, Thiele, Geoffrey M, Nelson, Amy J, Niu, Meng, Guda, Chittibabu, Eudy, James D, Barry, Austin E, Wyatt, Todd A, Romberger, Debra J, Duryee, Michael J, England, Bryant R, Poole, Jill A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.02.2021; Public Library of Science (PLoS)
• Subjects: Agriculture; Animals; Arthritis, Experimental - immunology; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - physiopathology; Autoimmune Diseases - metabolism; Biology and Life Sciences; Complications and side effects; Disease Models, Animal; Dust - immunology; Genetic aspects; Health aspects; High-Throughput Screening Assays - methods; Inflammation - metabolism; Inflammation Mediators - metabolism; Lung - immunology; Lung - metabolism; Lung - pathology; Lung diseases; Lung Diseases - metabolism; Macrophages - metabolism; Male; Medicine and Health Sciences; Mice; Mice, Inbred DBA; Monocytes - metabolism; Myeloid-Derived Suppressor Cells - metabolism; Neutrophils - metabolism; Patient outcomes; Research and Analysis Methods; Respiratory tract infections; Rheumatoid arthritis; Risk factors; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0240707

Rheumatoid arthritis (RA)-associated lung disease is a leading cause of mortality in RA, yet the mechanisms linking lung disease and RA remain unknown. Using an established murine model of RA-associated lung disease combining collagen-induced arthritis (CIA) with organic dust extract (ODE)-induced airway inflammation, differences among lung immune cell populations were analyzed by single cell RNA-sequencing. Additionally, four lung myeloid-derived immune cell populations including macrophages, monocytes/macrophages, monocytes, and neutrophils were isolated by fluorescence cell sorting and gene expression was determined by NanoString analysis. Unsupervised clustering revealed 14 discrete clusters among Sham, CIA, ODE, and CIA+ODE treatment groups: 3 neutrophils (inflammatory, resident/transitional, autoreactive/suppressor), 5 macrophages (airspace, differentiating/recruited, recruited, resident/interstitial, and proliferative airspace), 2 T-cells (differentiating and effector), and a single cluster each of inflammatory monocytes, dendritic cells, B-cells and natural killer cells. Inflammatory monocytes, autoreactive/suppressor neutrophils, and recruited/differentiating macrophages were predominant with arthritis induction (CIA and CIA+ODE). By specific lung cell isolation, several interferon-related and autoimmune genes were disproportionately expressed among CIA and CIA+ODE (e.g. Oasl1, Oas2, Ifit3, Gbp2, Ifi44, and Zbp1), corresponding to RA and RA-associated lung disease. Monocytic myeloid-derived suppressor cells were reduced, while complement genes (e.g. C1s1 and Cfb) were uniquely increased in CIA+ODE mice across cell populations. Recruited and inflammatory macrophages/monocytes and neutrophils expressing interferon-, autoimmune-, and complement-related genes might contribute towards pro-fibrotic inflammatory lung responses following airborne biohazard exposures in setting of autoimmune arthritis and could be predictive and/or targeted to reduce disease burden.