| Title: |
Interleukin 27 is a novel cytokine with anti-inflammatory effects against spondyloarthritis through the suppression of Th17 responses. |
| Authors: |
Jouhault, Quentin, Cherqaoui, Bilade, Jobart-Malfait, Aude, Glatigny, Simon, Lauraine, Marc, Hulot, Audrey, Morelle, Guillaume, Hagege, Benjamin, Ermoza, Kétia, El Marjou, Ahmed, Izac, Brigitte, Saintpierre, Benjamin, Letourneur, Franck, Rémy, Séverine, Anegon, Ignacio, Boissier, Marie-Christophe, Chiocchia, Gilles, Breban, Maxime, Araujo, Luiza M. |
| Source: |
Frontiers in Immunology; 2/2/2023, Vol. 14, p1-14, 14p |
| Subject Terms: |
REGULATORY T cells, T helper cells, SPONDYLOARTHROPATHIES, T cells, CYTOKINES |
| Abstract: |
Introduction: Spondylarthritis (SpA) development in HLA-B27/human b2-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. 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. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
