TY - JOUR
T1 - Cutting edge
T2 - IL-27 attenuates autoimmune neuroinflammation via regulatory T Cell/Lag3-Dependent but IL-10-independent mechanisms in vivo
AU - Kim, Dongkyun
AU - Le, Hongnga T.
AU - Nguyen, Quang Tam
AU - Kim, Sohee
AU - Lee, Juyeun
AU - Min, Booki
N1 - Funding Information:
This work was supported National Multiple Sclerosis Society Grant RG1411-02051 and National Institutes of Health Grants AI125247 and AI121524 (to B.M.).
Publisher Copyright:
© 2019 by The American Association of Immunologists, Inc.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1800898
DO - 10.4049/jimmunol.1800898
M3 - Article
C2 - 30700587
AN - SCOPUS:85062385932
SN - 0022-1767
VL - 202
SP - 1680
EP - 1685
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -