Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis

Jones, Gareth W., Bombardieri, Michele, Greenhill, Claire J., McLeod, Louise, Nerviani, Alessandra, Rocher-Ros, Vidalba, Cardus, Anna, Williams, Anwen S. ORCID: https://orcid.org/0000-0001-6118-020X, Pitzalis, Costantino, Jenkins, Brendan J. and Jones, Simon A. ORCID: https://orcid.org/0000-0001-7297-9711 2015. Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis. Journal of Experimental Medicine 212 (11) , pp. 1793-1802. 10.1084/jem.20132307

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Abstract

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–deficient mice with inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS development in RA through control of effector

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > R Medicine (General)
Additional Information:	This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
Publisher:	Rockefeller University Press
ISSN:	0022-1007
Funders:	Arthritis Research UK
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	28 August 2015
Last Modified:	16 Dec 2023 15:44
URI:	https://orca.cardiff.ac.uk/id/eprint/78703

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