IL-25 promotes the function of CD4+CD25+ T regulatory cells and prolongs skin-graft survival in murine models

Int Immunopharmacol. 2015 Oct;28(2):931-7. doi: 10.1016/j.intimp.2015.03.036. Epub 2015 Apr 10.

Abstract

Interleukin (IL)-25, also known as IL-17E, belongs to the IL-17 family of cytokines. Unlike other IL-17 family members, IL-25 promotes Th2-type immune responses, stimulating IL-4, IL-5, and IL-13 production. Here, we employed murine models of skin graft to explore the role of IL-25 in suppression of graft rejection. We found that IL-25 expression is increased during allograft rejection, and allograft rejection was enhanced in IL-25 KO mice. IL-25 KO was associated with down-regulation of Foxp3 expression in CD4+ T cells. Further, while adoptive transfer of WT regulatory T cells (Tregs) protected against allograft rejection, adoptive transfer of IL-25 deficient Tregs failed to protect against allograft rejection. Exogenous IL-25 restored Foxp3 expression and Treg function in vitro. Moreover, IL-25 promoted phosphorylation of NFAT2. Thus, IL-25 may enhance Treg function by up-regulating NFAT2 phosphorylation. Our findings suggest that IL-25 can sustain Foxp3 expression, enhance the suppressive function of Tregs, and prolong skin-graft survival.

Keywords: Interleukin-25; NFAT2; Regulatory T cells; Skin transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Female
  • Forkhead Transcription Factors / immunology
  • Interleukins / genetics
  • Interleukins / immunology*
  • Male
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NFATC Transcription Factors / immunology
  • Skin Transplantation*
  • T-Lymphocytes, Regulatory / immunology*
  • Transplantation Tolerance / immunology*

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukins
  • Mydgf protein, mouse
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse