Abstract
IL-27 regulates immune responses in inflammation. The underlying mechanism of IL-27 functions has long been attributed to its ability to induce IL-10 production in activated CD4 T cells. In this study, we report that Foxp3+ regulatory T cells (Tregs) are the main target cells of IL-27, mediating its immunoregulatory functions in vivo. Systemically delivered IL-27 efficiently prevents the development of experimental autoimmune encephalomyelitis, an autoimmune inflammation in the CNS. However, it failed to do so upon Treg depletion. IL-27 signaling in Tregs was necessary, as transferring Tregs deficient in IL-27Rα or Lag3, a downstream molecule induced by IL-27, was unable to protect mice from experimental autoimmune encephalomyelitis. IL-27 efficiently induced IL-10 expression in CD4 T cells in vitro; however, we found no evidence supporting IL-27-induced IL-10 induction in CD4 T cells in vivo. Taken together, our results uncover an irreplaceable contribution of Tregs during IL-27-mediated control of inflammation.
Original language | English (US) |
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Pages (from-to) | 1680-1685 |
Number of pages | 6 |
Journal | Journal of Immunology |
Volume | 202 |
Issue number | 6 |
DOIs | |
State | Published - 2019 |
Funding
This work was supported National Multiple Sclerosis Society Grant RG1411-02051 and National Institutes of Health Grants AI125247 and AI121524 (to B.M.).
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology