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

Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10190-10195. doi: 10.1073/pnas.1703100114. Epub 2017 Sep 5.


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.

Keywords: Foxp3+ regulatory T cells; IL-27; Tr1 cells; autoimmunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology*
  • Central Nervous System / immunology
  • Drug Evaluation, Preclinical
  • Encephalomyelitis / drug therapy
  • Encephalomyelitis / immunology*
  • Forkhead Transcription Factors / metabolism
  • Interleukins / metabolism
  • Interleukins / therapeutic use
  • Mice, Transgenic
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism*
  • Receptors, Interleukin
  • T-Lymphocytes, Regulatory / metabolism*


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Il27 protein, mouse
  • Il27ra protein, mouse
  • Interleukins
  • Receptors, Cytokine
  • Receptors, Interleukin