TRAF6 Is Essential for Maintenance of Regulatory T Cells That Suppress Th2 Type Autoimmunity

Go Muto, Hitoshi Kotani, Taisuke Kondo, Rimpei Morita, Sanae Tsuruta, Takashi Kobayashi, Hervé Luche, Hans Joerg Fehling, Matthew Walsh, Yongwon Choi, Akihiko Yoshimura

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Regulatory T cells (Tregs) maintain immune homeostasis by limiting inflammatory responses. TRAF6 plays a key role in the regulation of innate and adaptive immunity by mediating signals from various receptors including the T-cell receptor (TCR). T cell-specific deletion of TRAF6 has been shown to induce multiorgan inflammatory disease, but the role of TRAF6 in Tregs remains to be investigated. Here, we generated Treg-specific TRAF6-deficient mice using Foxp3-Cre and TRAF6-flox mice. Treg-specific TRAF6-deficient (cKO) mice developed allergic skin diseases, arthritis, lymphadenopathy and hyper IgE phenotypes. Although TRAF6-deficient Tregs possess similar in vitro suppression activity compared to wild-type Tregs, TRAF6-deficient Tregs did not suppress colitis in lymphopenic mice very efficiently due to reduced number of Foxp3-positive cells. In addition, the fraction of TRAF6-deficient Tregs was reduced compared with wild-type Tregs in female cKO mice without inflammation. Moreover, adoptive transfer of Foxp3 + Tregs into Rag2-/- mice revealed that TRAF6-deficient Tregs converted into Foxp3- cells more rapidly than WT Tregs under lymphopenic conditions. Fate-mapping analysis also revealed that conversion of Tregs from Foxp3+ to Foxp3- (exFoxp3 cells) was accelerated in TRAF6-deficient Tregs. These data indicate that TRAF6 in Tregs plays important roles in the maintenance of Foxp3 in Tregs and in the suppression of pathogenic Th2 type conversion of Tregs.

Original languageEnglish
Article numbere74639
JournalPloS one
Volume8
Issue number9
DOIs
Publication statusPublished - 2013 Sep 13

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'TRAF6 Is Essential for Maintenance of Regulatory T Cells That Suppress Th2 Type Autoimmunity'. Together they form a unique fingerprint.

  • Cite this

    Muto, G., Kotani, H., Kondo, T., Morita, R., Tsuruta, S., Kobayashi, T., Luche, H., Fehling, H. J., Walsh, M., Choi, Y., & Yoshimura, A. (2013). TRAF6 Is Essential for Maintenance of Regulatory T Cells That Suppress Th2 Type Autoimmunity. PloS one, 8(9), [e74639]. https://doi.org/10.1371/journal.pone.0074639