Treg-specific IL-27Rα deletion uncovers a key role for IL-27 in Treg function to control autoimmunity

Jeongsu Do, Dongkyun Kim, Sohee Kim, Alice Valentin-Torres, Nina Dvorina, Eunjung Jang, Vivekananthan Nagarajavel, Tara M. Desilva, Xiaoxia Li, Angela H. Ting, Dario A.A. Vignali, Stephen A. Stohlman, William M. Baldwin, Booki Min*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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 IFNγ- 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.

Original languageEnglish (US)
Pages (from-to)10190-10195
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number38
DOIs
StatePublished - Sep 19 2017
Externally publishedYes

Keywords

  • Autoimmunity
  • Foxp3+ regulatory T cells
  • IL-27
  • Tr1 cells

ASJC Scopus subject areas

  • General

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