High-Throughput Analysis of Lung Immune Cells in a Combined Murine Model of Agriculture Dust-Triggered Airway Inflammation With Rheumatoid Arthritis

Authors

Rohit Gaurav, University of Nebraska Medical CenterFollow
Ted R. Mikuls, University of Nebraska Medical CenterFollow
Geoffrey M. Thiele, University of Nebraska Medical CenterFollow
Amy J. Nelson, University of Nebraska Medical CenterFollow
Meng Niu, University of Nebraska Medical CenterFollow
Chittibabu Guda, University of Nebraska Medical CenterFollow
James D. Eudy, University of Nebraska Medical CenterFollow
Austin E. Barry, University of Nebraska Medical CenterFollow
Todd A. Wyatt, twyatt@unmc.eduFollow
Debra J. Romberger, University of Nebraska Medical CenterFollow
Michael J. Duryee, University of Nebraska Medical CenterFollow
Bryant R. England, University of Nebraska Medical CenterFollow
Jill A. Poole, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

PLoS One

Publication Date

2021

Volume

16

Abstract

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.

DOI Link

10.1371/journal.pone.0240707

ISSN

1932-6203

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

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.; and Poole, Jill A., "High-Throughput Analysis of Lung Immune Cells in a Combined Murine Model of Agriculture Dust-Triggered Airway Inflammation With Rheumatoid Arthritis" (2021). Journal Articles: Internal Medicine. 17.
https://digitalcommons.unmc.edu/com_internal_articles/17