Inflammation negatively regulates FOXP3 and regulatory T-cell function via DBC1

Yayi Gao, Jiayou Tang, Weiqian Chen, Qiang Li, Jia Nie, Fang Lin, Qingsi Wu, Zuojia Chen, Zhimei Gao, Huimin Fan, Andy Tsun, Jijia Shen, Guihua Chen, Zhongmin Liu, Zhenkun Lou, Nancy J. Olsen, Song Guo Zheng, Bin Li

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Forkhead box P3 (FOXP3)-positive Treg cells are crucial for maintaining immune homeostasis. FOXP3 cooperates with its binding partners to elicit Treg cells' signature and function, but the molecular mechanisms underlying the modulation of the FOXP3 complex remain unclear. Here we report that Deleted in breast cancer 1 (DBC1) is a key subunit of the FOXP3 complex. We found that DBC1 interacts physically with FOXP3, and depletion of DBC1 attenuates FOXP3 degradation in inflammatory conditions. Treg cells from Dbc1-deficient mice were more resistant to inflammation-mediated abrogation of Foxp3 expression and function and delayed the onset and severity of experimental autoimmune encephalomyelitis and colitis in mice. These findings establish a previously unidentified mechanism regulating FOXP3 stability during inflammation and reveal a pathway for potential therapeutic modulation and intervention in inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)E3246-E3254
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number25
DOIs
StatePublished - Jun 23 2015

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Regulatory T-Lymphocytes
Breast Neoplasms
Inflammation
Autoimmune Experimental Encephalomyelitis
Colitis
Homeostasis
Therapeutics

Keywords

  • Deleted in breast cancer 1
  • Foxp3 complex
  • Inflammation
  • Regulatory T cells

ASJC Scopus subject areas

  • General

Cite this

Inflammation negatively regulates FOXP3 and regulatory T-cell function via DBC1. / Gao, Yayi; Tang, Jiayou; Chen, Weiqian; Li, Qiang; Nie, Jia; Lin, Fang; Wu, Qingsi; Chen, Zuojia; Gao, Zhimei; Fan, Huimin; Tsun, Andy; Shen, Jijia; Chen, Guihua; Liu, Zhongmin; Lou, Zhenkun; Olsen, Nancy J.; Zheng, Song Guo; Li, Bin.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 25, 23.06.2015, p. E3246-E3254.

Research output: Contribution to journalArticle

Gao, Y, Tang, J, Chen, W, Li, Q, Nie, J, Lin, F, Wu, Q, Chen, Z, Gao, Z, Fan, H, Tsun, A, Shen, J, Chen, G, Liu, Z, Lou, Z, Olsen, NJ, Zheng, SG & Li, B 2015, 'Inflammation negatively regulates FOXP3 and regulatory T-cell function via DBC1', Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 25, pp. E3246-E3254. https://doi.org/10.1073/pnas.1421463112
Gao, Yayi ; Tang, Jiayou ; Chen, Weiqian ; Li, Qiang ; Nie, Jia ; Lin, Fang ; Wu, Qingsi ; Chen, Zuojia ; Gao, Zhimei ; Fan, Huimin ; Tsun, Andy ; Shen, Jijia ; Chen, Guihua ; Liu, Zhongmin ; Lou, Zhenkun ; Olsen, Nancy J. ; Zheng, Song Guo ; Li, Bin. / Inflammation negatively regulates FOXP3 and regulatory T-cell function via DBC1. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 25. pp. E3246-E3254.
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