title: Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis.
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 T cells. These studies open new opportunities for patient stratification and treatment.
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF10 3XQ, Wales, UK JonesSA@cf.ac.uk JonesGW6@cf.ac.uk.
authors.forename: Gareth W
authors.initials: GW
authors.lastname: Jones
authors.affiliation: 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.
authors.forename: Michele
authors.initials: M
authors.lastname: Bombardieri
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF10 3XQ, Wales, UK.
authors.forename: Claire J
authors.initials: CJ
authors.lastname: Greenhill
authors.affiliation: Centre for Innate Immunity and Infectious Diseases, Hudson (formerly Monash) Institute of Medical Research, Clayton, Victoria 3168, Australia.
authors.forename: Louise
authors.initials: L
authors.lastname: McLeod
authors.affiliation: 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.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nerviani
authors.affiliation: 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.
authors.forename: Vidalba
authors.initials: V
authors.lastname: Rocher-Ros
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF10 3XQ, Wales, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Cardus
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF10 3XQ, Wales, UK.
authors.forename: Anwen S
authors.initials: AS
authors.lastname: Williams
authors.affiliation: 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.
authors.forename: Costantino
authors.initials: C
authors.lastname: Pitzalis
authors.affiliation: Centre for Innate Immunity and Infectious Diseases, Hudson (formerly Monash) Institute of Medical Research, Clayton, Victoria 3168, Australia.
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Jenkins
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF10 3XQ, Wales, UK JonesSA@cf.ac.uk JonesGW6@cf.ac.uk.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Jones
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology*; D002478:Cells, Cultured; D006801:Humans; D007378:Interleukins / Q000502:physiology*; D008221:Lymphoid Tissue / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018123:Receptors, Interleukin / Q000032:analysis; D050796:STAT3 Transcription Factor / Q000502:physiology; D013585:Synovitis / Q000276:immunology
chemical_list: C112441:IL27RA protein, human; D007378:Interleukins; C464565:MYDGF protein, human; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor