Frontiers in Immunology (Feb 2023)

Interleukin 27 is a novel cytokine with anti-inflammatory effects against spondyloarthritis through the suppression of Th17 responses

  • Quentin Jouhault,
  • Quentin Jouhault,
  • Bilade Cherqaoui,
  • Bilade Cherqaoui,
  • Aude Jobart-Malfait,
  • Aude Jobart-Malfait,
  • Simon Glatigny,
  • Simon Glatigny,
  • Marc Lauraine,
  • Marc Lauraine,
  • Audrey Hulot,
  • Audrey Hulot,
  • Guillaume Morelle,
  • Guillaume Morelle,
  • Benjamin Hagege,
  • Benjamin Hagege,
  • Kétia Ermoza,
  • Kétia Ermoza,
  • Ahmed El Marjou,
  • Brigitte Izac,
  • Benjamin Saintpierre,
  • Franck Letourneur,
  • Séverine Rémy,
  • Ignacio Anegon,
  • Marie-Christophe Boissier,
  • Gilles Chiocchia,
  • Gilles Chiocchia,
  • Gilles Chiocchia,
  • Maxime Breban,
  • Maxime Breban,
  • Maxime Breban,
  • Luiza M. Araujo,
  • Luiza M. Araujo

DOI
https://doi.org/10.3389/fimmu.2022.1072420
Journal volume & issue
Vol. 13

Abstract

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IntroductionSpondylarthritis (SpA) development in HLA-B27/human β2-microglobulin transgenic rat (B27-rat) is correlated with altered conventional dendritic cell (cDC) function that promotes an inflammatory pattern of CD4+T cells, including a biased expansion of pro-inflammatory Th17 population and imbalance of regulatory T cells cytokine profile. Transcriptomic analysis revealed that cDCs from B27-rats under express IL-27, an anti-inflammatory cytokine which induces the differentiation of IL-10+ regulatory T cells and inhibits Th17 cells.MethodsHere, we first investigated whether in vitro addition of exogenous IL-27 could reverse the inflammatory pattern observed in CD4+ T cells. Next, we performed preclinical assay using IL-27 to investigate whether in vivo treatment could prevent SpA development in B27-rats.Resultsin vitro addition of IL-27 to cocultures of cDCs and CD4+ T cell subsets from B27-rats reduced IL-17 and enhanced IL-10 production by T cells. Likewise, IL-27 inhibited the production of IL-17 by CD4+ T cells from SpA patients. Interestingly, in vivo treatment with recombinant IL-27 starting before SpA onset, inhibited SpA development in B27-rats through the suppression of IL-17/TNF producing CD4+ T cells.DiscussionOverall, our results reveal a potent inhibitory effect of IL-27 and highlight this cytokine as a promising new therapeutic target in SpA, especially for SpA patients non responders to currently approved biotherapies.

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