{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:13:19Z","timestamp":1783570399072,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5K08HL161258"],"award-info":[{"award-number":["5K08HL161258"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5P50AR060812"],"award-info":[{"award-number":["5P50AR060812"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Rheumatoid arthritis (RA) often involves extra\u2010articular complications, including interstitial lung disease (ILD) and\/or pulmonary nodules. Transcriptomic profiling of lung tissue provides the opportunity to directly assess cell\u2010specific gene expression and corresponding pathway activation in different types of rheumatoid lung disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used probe\u2010based, Flex single\u2010cell RNA sequencing (scRNA\u2010seq) of fixed lung tissue specimens to compare gene expression profiles in macrophage and fibroblast populations contributing to tissue remodeling in RA\u2010associated ILD (RA\u2010ILD) versus RA lung nodules. Additional comparison of differentially expressed genes (DEGs) in lung tissue explants from patients with idiopathic pulmonary fibrosis (IPF) elucidated the degree of overlap with RA\u2010ILD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Flex scRNA\u2010seq of lung specimens from controls without disease (n = 4) and patients with RA\u2010ILD (n = 9) or RA nodules (n = 3) yielded clustering profiles mirroring uniform manifold approximation and projection distributions from conventional poly(A) capture\u2013based scRNA\u2010seq of RA\u2010ILD, IPF, and control lung tissue. Comparative transcriptional profiling of macrophage and fibroblast subpopulations in RA\u2010ILD and RA lung nodules revealed only partial overlap, with differential up\u2010regulation of immunoregulatory, angioregulatory, and matrix assembly pathways in RA\u2010ILD fibroblasts that contrasted with selective up\u2010regulation of pathways promoting innate and adaptive immunity in macrophage populations comprising RA lung nodules. Comparison of DEGs between RA\u2010ILD and IPF lung\u2010derived macrophage and fibroblast populations demonstrated significant enhancement of profibrotic gene expression in both disease states.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Flex scRNA\u2010seq of pulmonary macrophage and fibroblast subpopulations reveals key differences in transcriptional profile, distinguishing RA\u2010ILD from RA lung nodules. Parallel comparison of cell type\u2013specific gene expression profiles between RA\u2010ILD and IPF demonstrates significant overlap in profibrotic transcriptional programs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70256","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T12:05:44Z","timestamp":1782129944000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Transcriptional Profiling of Key Macrophage and Fibroblast Subpopulations in Rheumatoid Arthritis\u2013Associated Lung Disease"],"prefix":"10.1002","author":[{"given":"Tracy","family":"Tabib","sequence":"first","affiliation":[{"name":"Center for Systems Immunology University of Pittsburgh  Pittsburgh 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Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sembrat","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Cody","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5747-064X","authenticated-orcid":false,"given":"Jishnu","family":"Das","sequence":"additional","affiliation":[{"name":"Center for Systems Immunology University of Pittsburgh  Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Lafyatis","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1387-0860","authenticated-orcid":false,"given":"Dana P.","family":"Ascherman","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology University of Pittsburgh School of Medicine  Pittsburgh 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