Interleukin 27 is a novel cytokine with anti-inflammatory effects against spondyloarthritis through the suppression of Th17 responses
Quentin Jouhault, Bilade Cherqaoui, Aude Jobart‐Malfait, Simon Glatigny, Marc Lauraine, Audrey Hulot, Guillaume Morelle, Benjamin Hagège, Kétia Ermoza, Ahmed El Marjou, Brigitte Izac, Benjamin Saintpierre, Franck Letourneur, Séverine Remy, Ignacio Anegón, Marie‐Christophe Boissier, Gilles Chiocchia, Maxime Bréban, Luiza M. Araujo
Abstract
Introduction Spondylarthritis (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 Th 17 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 Th 17 cells. Methods Here, 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. Results in 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. Discussion Overall, 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.