{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:39:01Z","timestamp":1792813141021,"version":"4.5.0"},"reference-count":81,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Interstitial lung disease (ILD) is a well-known extra-articular manifestation of rheumatoid arthritis (RA). RA-associated ILD (RA-ILD) exists on a wide spectrum, with variable levels of inflammatory and fibrotic activity, although all subtypes are regarded as irreversible pathologic conditions. In both articular and pulmonary manifestations, TNF is a significant pathogenic factor. Whereas anti-TNF therapy alleviates joint pathologic conditions, it exacerbates fibrotic RA-ILD. The TNF-transgenic (TNF-Tg) murine model of RA develops both inflammatory arthritis and an ILD that mimics a cellular nonspecific interstitial pneumonia pattern dominated by an interstitial accumulation of inflammatory cells with minimal-to-absent fibrosis. Given the model\u2019s potential to elucidate the genesis of inflammatory RA-ILD, we aim to achieve the following: 1) characterize the cellular accumulations in TNF-Tg lungs, and 2) assess the reversibility of inflammatory ILD following anti-TNF therapy known to resolve TNF-Tg inflammatory arthritis. TNF-Tg mice with established disease were randomized to anti-TNF or placebo therapy and evaluated with imaging, histology, and flow cytometric analyses, together with wild-type controls. Flow cytometry of TNF-Tg versus wild-type lungs revealed significant increases in activated monocytes, conventional dendritic cells, and CD21+\/CD23\u2212 B cells that are phenotypically distinct from the B cells in inflamed nodes, which are known to accumulate in joint-draining lymph nodes. In contrast to human RA-ILD, anti-TNF treatment significantly alleviated both joint and lung inflammation. These results identify a potential role for activated monocytes, conventional dendritic cells, and CD21+\/CD23\u2212 B cells in the genesis of RA-ILD, which exist in a previously unknown, reversible, prefibrotic stage of the disease.<\/jats:p>","DOI":"10.4049\/jimmunol.1900473","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T20:34:08Z","timestamp":1572294848000},"page":"2837-2849","source":"Crossref","is-referenced-by-count":34,"title":["TNF-Induced Interstitial Lung Disease in a Murine Arthritis Model: Accumulation of Activated Monocytes, Conventional Dendritic Cells, and CD21+\/CD23\u2212 B Cell Follicles Is Prevented with Anti-TNF Therapy"],"prefix":"10.1093","volume":"203","author":[{"given":"Emily K","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"},{"name":"Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2333-2863","authenticated-orcid":false,"given":"Zoe I","family":"Henkes","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0463-5823","authenticated-orcid":false,"given":"Brion","family":"McGowan","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D","family":"Bell","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"},{"name":"Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moises J","family":"Velez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4511-8363","authenticated-orcid":false,"given":"Alexandra M","family":"Livingstone","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"},{"name":"David H. Smith Center for Vaccine Biology and Immunology, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2602-1219","authenticated-orcid":false,"given":"Christopher T","family":"Ritchlin","sequence":"additional","affiliation":[{"name":"Allergy, Immunology, and Rheumatology, Department of Medicine, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4854-9698","authenticated-orcid":false,"given":"Edward M","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"},{"name":"Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"},{"name":"Department of Orthopaedics and Rehabilitation, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4028-7723","authenticated-orcid":false,"given":"Homaira","family":"Rahimi","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"},{"name":"Department of Pediatrics, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,12,1]]},"reference":[{"key":"2025030417544390900_r1","first-page":"S295","article-title":"Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis","volume":"18","author":"Gibofsky","year":"2012","journal-title":"Am. 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