| First Author | Do J | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 38 | Pages | 10190-10195 |
| PubMed ID | 28874534 | Mgi Jnum | J:253624 |
| Mgi Id | MGI:6095004 | Doi | 10.1073/pnas.1703100114 |
| Citation | Do J, et al. (2017) Treg-specific IL-27Ralpha deletion uncovers a key role for IL-27 in Treg function to control autoimmunity. Proc Natl Acad Sci U S A 114(38):10190-10195 |
| abstractText | Dysregulated Foxp3(+) Treg functions result in uncontrolled immune activation and autoimmunity. Therefore, identifying cellular factors modulating Treg functions is an area of great importance. Here, using Treg-specific Il27ra(-/-) mice, we report that IL-27 signaling in Foxp3(+) Tregs is essential for Tregs to control autoimmune inflammation in the central nervous system (CNS). Following experimental autoimmune encephalomyelitis (EAE) induction, Treg-specific Il27ra(-/-) mice develop more severe EAE. Consistent with the severe disease, the numbers of IFNgamma- and IL-17-producing CD4 T cells infiltrating the CNS tissues are greater in these mice. Treg accumulation in the inflamed CNS tissues is not affected by the lack of IL-27 signaling in Tregs, suggesting a functional defect of Il27ra(-/-) Tregs. IL-10 production by conventional CD4 T cells and their CNS accumulation are rather elevated in Treg-specific Il27ra(-/-) mice. Analysis with Treg fate-mapping reporter mice further demonstrates that IL-27 signaling in Tregs may control stability of Foxp3 expression. Finally, systemic administration of recombinant IL-27 in Treg-specific Il27ra(-/-) mice fails to ameliorate the disease even in the presence of IL-27-responsive conventional CD4 T cells. These findings uncover a previously unknown role of IL-27 in regulating Treg function to control autoimmune inflammation. |
