{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T07:52:49Z","timestamp":1790927569415,"version":"4.1.0"},"reference-count":35,"publisher":"The Korean Academy of Tuberculosis and Respiratory Diseases","issue":"4","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Korean Academy of Tuberculosis and Respiratory Diseases","award":["KBA24008"],"award-info":[{"award-number":["KBA24008"]}]}],"content-domain":{"domain":["e-trd.org"],"crossmark-restriction":true},"short-container-title":["Tuberc Respir Dis"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:p>Background: Interstitial lung disease (ILD) is a common but serious extra-articular manifestation of rheumatoid arthritis (RA). RA-associated ILD (RA-ILD), which often presents with the usual interstitial pneumonia pattern, can resemble idiopathic pulmonary fibrosis (IPF), though the treatment and progression of these two conditions differ. However, the immunologic and molecular mechanisms associated with RA-ILD and IPF development have not been well elucidated at the single-cell level.Methods: To investigate the underlying mechanisms associated with RA-ILD and IPF development, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from five RA-ILD patients and five patients with IPF with a matched age and sex distribution.Results: A high-quality scRNA-seq dataset comprising 31,416 peripheral immune cells was generated. Overall immune composition was similar between groups; however, a significant elevation of natural killer (NK) cells was seen among the RA-ILD PBMCs, with increased expression of cytotoxic and inflammation-related genes (GZMB, GZMH, PRF1) as well as interferon\u2011related genes (STAT1, STAT3, IRF9, IFNG). Myeloid subsets displayed distinct transcriptional programs in IPF and RA-ILD: IPF CD16+ monocytes were enriched for transforming growth factor beta (TGF\u2011\u03b2)\u2013driven fibrotic signaling, whereas RA-ILD monocytes exhibited type I\/II interferon pathway activation. Fibrosis\u2011related genes (TGFB1, SMAD3, SMAD7, TGIF1) were specifically upregulated in IPF.Conclusion: RA\u2011ILD and IPF share similar peripheral immune cell compositions, but exhibit distinct transcriptional activation patterns. RA\u2011ILD is characterized by increased NK\u2011cell\u2013driven cytotoxic and interferon\u2011related responses, along with interferon\u2011activated monocytes. In contrast, IPF shows a TGF\u2011\u03b2\u2013dominant fibrotic program, with transcriptional activation of CD16+ monocytes and upregulation of fibrosis\u2011related genes.<\/jats:p>","DOI":"10.4046\/trd.2026.0085","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T02:05:23Z","timestamp":1785290723000},"page":"542-552","update-policy":"https:\/\/doi.org\/10.4046\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-Cell Analysis Identifies Factors Associated with Rheumatoid Arthritis-Related Interstitial Lung Disease in Comparison with Idiopathic Pulmonary Fibrosis"],"prefix":"10.4046","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3670-8890","authenticated-orcid":true,"given":"Dongjun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea"},{"name":"Cancer Research Institute, Seoul National 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Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4467-0949","authenticated-orcid":true,"given":"Hyun Je","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea"},{"name":"Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea"},{"name":"Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0800-4324","authenticated-orcid":true,"given":"Bo-Guen","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of 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