{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:59:07Z","timestamp":1790499547370,"version":"4.1.0"},"reference-count":33,"publisher":"Rockefeller University Press","issue":"11","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,10,19]]},"abstract":"<jats:p>Ectopic lymphoid-like structures (ELSs) reminiscent of secondary lymphoid organs often develop at sites of chronic inflammation where they contribute to immune-mediated pathology. Through evaluation of synovial tissues from rheumatoid arthritis (RA) patients, we now show that low interleukin-27 (IL-27) expression corresponds with an increased incidence of ELS and gene signatures associated with their development and activity. The presence of synovial ELS was also noted in mice deficient in the IL-27 receptor (IL-27R) after the onset of inflammatory arthritis. Here, pathology was associated with increased synovial expression of pro-inflammatory cytokines, homeostatic chemokines, and transcriptional regulators linked with lymphoid neogenesis. In both clinical and experimental RA, synovial ELS coincided with the heightened local expression of cytokines and transcription factors of the Th17 and T follicular helper (Tfh) cell lineages, and included podoplanin-expressing T cells within lymphoid aggregates. IL-27 inhibited the differentiation of podoplanin-expressing Th17 cells, and an increased number of these cells were observed in IL-27R\u2013deficient mice with inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS development in RA through control of effector T cells. These studies open new opportunities for patient stratification and treatment.<\/jats:p>","DOI":"10.1084\/jem.20132307","type":"journal-article","created":{"date-parts":[[2015,9,29]],"date-time":"2015-09-29T01:58:58Z","timestamp":1443491938000},"page":"1793-1802","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":101,"title":["Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis"],"prefix":"10.1084","volume":"212","author":[{"given":"Gareth W.","family":"Jones","sequence":"first","affiliation":[{"name":"Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF10 3XQ, Wales, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Bombardieri","sequence":"additional","affiliation":[{"name":"Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, John Vane Science Centre, London EC1M 6BQ, England, UK 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire J.","family":"Greenhill","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF10 3XQ, Wales, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"McLeod","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases, Hudson (formerly Monash) Institute of Medical Research, Clayton, Victoria 3168, Australia 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Nerviani","sequence":"additional","affiliation":[{"name":"Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, John Vane Science Centre, London EC1M 6BQ, England, UK 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidalba","family":"Rocher-Ros","sequence":"additional","affiliation":[{"name":"Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, John Vane Science Centre, London EC1M 6BQ, England, UK 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Cardus","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF10 3XQ, Wales, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwen S.","family":"Williams","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF10 3XQ, Wales, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costantino","family":"Pitzalis","sequence":"additional","affiliation":[{"name":"Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, John Vane Science Centre, London EC1M 6BQ, England, UK 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan J.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases, Hudson (formerly Monash) Institute of Medical Research, Clayton, Victoria 3168, Australia 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon A.","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF10 3XQ, Wales, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2015,9,28]]},"reference":[{"key":"2023072602375974000_bib1","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1084\/jem.20020619","article-title":"A point mutation of Tyr-759 in interleukin 6 family cytokine receptor subunit gp130 causes autoimmune arthritis","volume":"196","author":"Atsumi","year":"2002","journal-title":"J. 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