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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.\n                    <jats:italic>Oasl1<\/jats:italic>\n                    ,\n                    <jats:italic>Oas2<\/jats:italic>\n                    ,\n                    <jats:italic>Ifit3<\/jats:italic>\n                    ,\n                    <jats:italic>Gbp2<\/jats:italic>\n                    ,\n                    <jats:italic>Ifi44<\/jats:italic>\n                    , and\n                    <jats:italic>Zbp1<\/jats:italic>\n                    ), corresponding to RA and RA-associated lung disease. Monocytic myeloid-derived suppressor cells were reduced, while complement genes (e.g.\n                    <jats:italic>C1s1<\/jats:italic>\n                    and\n                    <jats:italic>Cfb<\/jats:italic>\n                    ) 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.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0240707","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T16:49:59Z","timestamp":1613148599000},"page":"e0240707","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["High-throughput analysis of lung immune cells in a combined murine model of agriculture dust-triggered airway inflammation with rheumatoid arthritis"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4753-2680","authenticated-orcid":true,"given":"Rohit","family":"Gaurav","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ted R.","family":"Mikuls","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey M.","family":"Thiele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy J.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Niu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chittibabu","family":"Guda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James 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