The contribution from interleukin-27 towards rheumatoid inflammation: insights from gene expression.
Journal
Genes and immunity
ISSN: 1476-5470
Titre abrégé: Genes Immun
Pays: England
ID NLM: 100953417
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
22
12
2019
accepted:
26
05
2020
revised:
09
05
2020
pubmed:
11
6
2020
medline:
26
5
2021
entrez:
11
6
2020
Statut:
ppublish
Résumé
We aimed to assess expression of genes encoding the heterodimeric IL-27 cytokine and constituent subunits of the Il-27 receptor in rheumatoid arthritis (RA), including in extra-articular, subcutaneous rheumatoid nodules. Comparing between nodules and joint synovia, significantly elevated expression of IL27A within nodules, and comparable IL27B expression, identified nodules as a significant source of IL-27 in RA. T-lymphocytes were the main source of IL27RA transcript, and IL27RA expression correlated with a number of plasma cytokines, as well as tissue TNF expression in both nodules and RA synovia. In synovia, correlations between IL27A, IL27RA IL17A and CD21L expression, and significantly elevated expression of the genes encoding IL-27, associated the presence of IL-27 with B cell-dominated synovial inflammation. Impact from nodule derived IL-27 on systemic or synovial inflammation in RA remains unknown and further study of these implications is required. Our study raises questions regarding the appropriate circumstances for the blockade or administration of IL-27 as a potential therapeutic adjunct in RA.
Identifiants
pubmed: 32518420
doi: 10.1038/s41435-020-0102-z
pii: 10.1038/s41435-020-0102-z
doi:
Substances chimiques
IL17A protein, human
0
Interleukin-17
0
Interleukins
0
MYDGF protein, human
0
Receptors, Complement 3d
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
249-259Références
Bastian D, Wu Y, Betts BC, Yu XZ. The IL-12 cytokine and receptor family in graft-vs-host disease. Front Immunol. 2019;10:988. https://doi.org/10.3389/fimmu.2019.00988 .
doi: 10.3389/fimmu.2019.00988
pubmed: 31139181
pmcid: 6518430
Stumhofer JS, Tait ED, Quinn WJ, Hosken N, Spudy B, Goenka R, et al. A role for Il-27p28 as an antagonist of gp130-mediated signalling. Nat Immunol. 2010;11:1119–26.
doi: 10.1038/ni.1957
Pflanz S, Timans JC, Cheung J, Rosales R, Kanzler H, Hibbert L, et al. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naïve CD4
doi: 10.1016/S1074-7613(02)00324-2
Petes C, Mariani MK, Yang Y, Grandvaux N, Gee K. Interleukin (IL)-6 inhibits IL-27- and IL-30-mediated inflammatory responses in human monocytes. Front Immunol. 2018;9:256. https://doi.org/10.3389/fimmu.2018.00256 .
doi: 10.3389/fimmu.2018.00256
pubmed: 29497424
pmcid: 5818456
Muller SI, Friedl A, Aschenbrenner I, Esser-von Bieren J, Zacharias M, Devergne O, et al. A folding switch regulates interleukin biogenesis and secretion of it α-subunit as a cytokine. Proc Nat Acad Sci USA. 2019;116:1585–90.
doi: 10.1073/pnas.1816698116
Laroni A, Gandhi R, Beynon V, Weiner HL. IL-27 imparts immunoregulatory function to human NK cells subsets. PLoS ONE. 6:e26173. https://doi.org/10.1371/journal.pone.0026173 .
Jankowski M, Kopinski P, Goc A. Interleukin-27: biological properties and clinical application. Arch Immunol Ther Exp. 2010;58:417–25.
doi: 10.1007/s00005-010-0098-6
Wong CK, Chen DP, Tam LS, Li EK, Yin YB, Lam CW. Effects of inflammatory cytokineIL-27 on the activation of fibroblast-like synoviocytes in rheumatoid arthritis. Arth Res Ther. 2010;12:R129.
doi: 10.1186/ar3067
Goldberg R, Wildbaum G, Zohar Y, Maor G, Karin N. Suppression of ongoing adjuvant-induced arthritis by neutralising the function of the p28 subunit of IL-27. J Immunol. 2004;173:1171–8.
doi: 10.4049/jimmunol.173.2.1171
Jones GW, Bombardieri M, Greenhill CJ, McLeod L, Nerviani A, Rocher-Ros V, et al. Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis. J Exp Med. 2015;212:1793–802.
doi: 10.1084/jem.20132307
Shen H, Xia L, Xiao W, Lu J. Increased levels of interleukin-27 in patients with rheumatoid arthritis. Arth Rheum. 2011;63:860–1.
doi: 10.1002/art.30180
Tanida S, Yoshitomi H, Ishikawa M, Kasahara T, Murata, Shibuya H, et al. IL-27-producing CD14(+) cells infiltrate inflamed joints of rheumatoid arthritis and regulate inflammation and chemotactic migration. Cytokine. 2011;55:237–44.
doi: 10.1016/j.cyto.2011.04.020
Baker KF, Skelton AJ, Lendrem DW, Scadeng A, Thompson B, Pratt AG, et al. Predicting drug-free remission in rheumatoid arthritis: a prospective interventional cohort study. J Autoimmun. 2019;105:102298.
doi: 10.1016/j.jaut.2019.06.009
Hessian PA, Highton J, Kean A, Sun CK, Chin M. Cytokine profile of the rheumatoid nodule suggests that it is a Th1 granuloma. Arth Rheum. 2003;48:334–8.
doi: 10.1002/art.10776
Dorosz SA, Ginolhac A, Kahne T, Naumann M, Salamann Sauter T. et al. Role of calprotectin as a modulator of the IL27-mediated proinflammatory effect on endothelial cells. Mediators Inflamm. 2015;2015:737310.
doi: 10.1155/2015/737310
McKelvey KJ, Millier MJ, Doyle TC, Stamp LK, Highton J, Hessian PA. Co-expression of CD21l and IL17A defines a subset of rheumatoid synovia, characterised by large lymphoid aggregates and high inflammation. PLoS ONE. 2018;16:e0202135.
doi: 10.1371/journal.pone.0202135
Humby F, Bombardieri M, Manzo A, Kelly S, Blades MC, Kirkham B, et al. Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium. PLoS Med. 2009;6:e1.
doi: 10.1371/journal.pmed.0060001
Palmer DG, Hogg N, Denholm I, Allen CA, Highton J, Hessian PA. Comparison of phenotype expression by mononuclear phagocytes within subcutaneous gouty tophi and rheumatoid nodules. Rheumatol Int. 1987;7:187–93.
doi: 10.1007/BF00541376
Soni S, O’Dea KP, Tan YY, Cho K, Abe E, Romano R, et al. ATP directs cytokine trafficking and promotes novel membrane TNF signalling via micro-vesicles. FASEB J. 2019;33:6442–55.
doi: 10.1096/fj.201802386R
Highton J, Hessian PA, Stamp L. The rheumatoid nodule: peripheral or central to rheumatoid arthritis. Rheumatology. 2007;46:1385–7.
doi: 10.1093/rheumatology/kem163
Highton J, Hung N, Hessian P, Wilsher M. Pulmonary rheumatoid nodules demonstrating features usually associated with synovial membrane. Rheumatology. 2007;46:811–4.
doi: 10.1093/rheumatology/kel411
Stamp LK, Eason A, Lehnigk U, Highton J, Hessian PA. Different T cell subsets in the nodule and synovial membrane: absence of interleukin-17A in rheumatoid nodules. Arth Rheum. 2008;58:1601–8.
doi: 10.1002/art.23455
Liu H, Rohowsky-Kochan C. Interleukin-27-mediated suppression of human Th17 cells is associated with activation of STAT1 and suppressor of cytokine signalling protein 1. J Interferon Cytokine Res. 2011;31:459–69.
doi: 10.1089/jir.2010.0115
Larousserie F, Pflanz S, Coulomb-L’Hermine A, Brousse N, Kastelein R, Cevergne O. Expression of IL-27 in human Th1-associated granulomatous diseases. J Path. 2004;202:164–71.
doi: 10.1002/path.1508
Cao Y, Doodes PD, Glant TT, Finnegan A. IL-27 induces a Th1 immune response and susceptibility to experimental arthritis. J Immunol. 2008;180:922–30.
doi: 10.4049/jimmunol.180.2.922
Gong F, Pan Y-H, Huang X, Chen J, Xiao J, Zhu H. Interleukin-27 as a potential therapeutic target for rheumatoid arthritis: has the time come? Clin Rheumatol. 2013;32:1425–8.
doi: 10.1007/s10067-013-2341-0
Jones GW, Hill DG, Cardua A, Jones SA. Il-27: a double agent in the IL-6 family. Clin Exp Immunol. 2018;193:37–46.
doi: 10.1111/cei.13116
Canete JD, Celis R, Yeremenko N, Sanmarti R, van Duivenvoorde L, Ramirez J, et al. Ectopic lymphoid neogenesis is strongly associated with activation of the IL-23 pathway in rheumatoid synovitis. Arth Res Ther. 2015;17:173. https://doi.org/10.1186/s13075-015-0688-0 .
doi: 10.1186/s13075-015-0688-0
Batten M, Ramamoorrthi N, Kijavin NM, Ma CS, Cox J, Dengler HS, et al. IL-27 supports germinal centre function by enhancing IL-21 production and the function of T follicular helper cells. J Exp Med. 2010;201:2895–906.
doi: 10.1084/jem.20100064
Vijayan D, Mohd Redzwan N, Avery DT, Wirasinha RC, Brink R, Walters G, et al. IL-27 directly enhances germinal centre B cell activity and potentiates Lupus in sanroque mice. J Immunol. 2016;197:3008–17.
doi: 10.4049/jimmunol.1600652
Wang RX, Yu CR, Dambuza IM, Mahdi RM, Dolinska MB, Sergeev YV, et al. Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nat Med. 2014;20:633–41.
doi: 10.1038/nm.3554
Villarino AV, Larkin J, Saris CJ, Caton AJ, Lucas S, Wong T, et al. Positive and negative regulation of the IL-27 receptor during lymphoid cell activation. J Immunol. 2005;15:7684–91.
doi: 10.4049/jimmunol.174.12.7684
Mehta AK, Gracias DT, Croft M. TNF activity and T cells. Cytokine. 2018;101:14–18.
doi: 10.1016/j.cyto.2016.08.003
Millier MJ, Stamp LK, Hessian PA. Digital-PCR for gene expression: Impact from inherent tissue RNA degradation. Sci Rep. 2018;7:17235. https://doi.org/10.1038/s41598-017-17619-0 .
doi: 10.1038/s41598-017-17619-0