This study shows that, instead of directly affecting T cells as was previously thought, interleukin-27 (IL-27) modulates dendritic cells (DCs) to suppress T cells. Pretreatment of DCs with IL-27 decreased their ability to promote the differentiation of T helper 1 (TH1) and TH17 cells and increased their ability to generate regulatory T cells. Consistent with the increased induction of pathogenic TH cell subsets, chimeric mice containing IL-27 receptor α-chain (IL-27RA)-deficient DCs developed faster onset and more severe experimental autoimmune encephalomyelitis (EAE) than control mice. Microarray analysis of IL-27-treated DCs showed upregulation of expression of CD39, which reduced extracellular concentrations of ATP and suppressed nucleotide-dependent activation of NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3). Finally, vaccination with IL-27-conditioned DCs suppressed EAE and reduced epitope spreading.
References
Mascanfroni, I. D. et al. IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39. Nature Immunol. http://dx.doi.org/10.1038/ni.2695 (2013)
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Bird, L. IL-27 induces immunosuppressive DCs. Nat Rev Immunol 13, 706 (2013). https://doi.org/10.1038/nri3545x
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DOI: https://doi.org/10.1038/nri3545x
