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Scientific article
Open access
English

Metallothioneins negatively regulate IL-27-induced type 1 regulatory T-cell differentiation

Publication date2013
Abstract

IL-27-induced type 1 regulatory T (Tr1) cells suppress autoimmunity by producing IL-10. Signal transducer and activator of transcription (STAT) 1 and STAT3 have been described as key transcription factors that promote IL-10 secretion from Tr1 cells induced by IL-27. However, the molecular pathways for negatively regulating Tr1 cell differentiation remain elusive. Here, we show that IL-27 induces metallothioneins (MTs) that in turn prevent Tr1 cell development. MT expression leads to the reduction of STAT1 and STAT3 phosphorylation under Tr1 differentiation condition, resulting in impaired IL-10 production. Accordingly, Tr1 cells derived from MT-deficient mice showed an increased ability to produce IL-10 and potently suppress experimental autoimmune encephalomyelitis upon adoptive transfer. Moreover, activation of STAT1 and/or STAT3 can overcome the suppression of IL-10 by MTs, indicating a dynamic balance between STATs and MTs in regulating IL-10 during Tr1 cell differentiation.

Keywords
  • Animals
  • Cell Differentiation
  • Cell Separation
  • Cells, Cultured
  • Encephalomyelitis, Autoimmune, Experimental/immunology
  • Flow Cytometry
  • Gene Expression Regulation
  • Humans
  • Interleukin-10/metabolism
  • Interleukin-17/metabolism
  • Metallothionein/metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphorylation
  • STAT1 Transcription Factor/metabolism
  • STAT3 Transcription Factor/metabolism
  • T-Lymphocytes, Regulatory/immunology/metabolism
Funding
  • Swiss National Science Foundation - PASMA—118720/1
Citation (ISO format)
WU, Chuan et al. Metallothioneins negatively regulate IL-27-induced type 1 regulatory T-cell differentiation. In: Proceedings of the National Academy of Sciences of the United States of America, 2013, vol. 110, n° 19, p. 7802–7807. doi: 10.1073/pnas.1211776110
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal0027-8424
550views
278downloads

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Creation10/31/2013 8:49:00 AM
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Update time03/14/2023 8:49:31 PM
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