Extracellular redox modulation by regulatory T cells

Nat Chem Biol. 2009 Oct;5(10):721-3. doi: 10.1038/nchembio.212. Epub 2009 Aug 30.

Abstract

We demonstrate that the mechanism of redox remodeling during mouse T-cell activation involves secretion of glutathione by dendritic cells and its subsequent cleavage to cysteine. Extracellular cysteine accumulation results in a lower redox potential, which is conducive to proliferation, and changes the net redox status of exofacial protein domains. Regulatory T cells inhibit this redox metabolite signaling pathway, which represents a previously unrecognized mechanism for immunosuppression of effector T cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Cysteine / metabolism*
  • Cysteine / pharmacology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Extracellular Space / metabolism*
  • Flow Cytometry
  • Glutathione / metabolism*
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Oxidation-Reduction
  • Signal Transduction / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Glutathione
  • Cysteine

Associated data

  • PubChem-Substance/85147453
  • PubChem-Substance/85147454
  • PubChem-Substance/85147455
  • PubChem-Substance/85147456
  • PubChem-Substance/85147457
  • PubChem-Substance/85147458
  • PubChem-Substance/85147459
  • PubChem-Substance/85147460
  • PubChem-Substance/85147461
  • PubChem-Substance/85147462
  • PubChem-Substance/85147463
  • PubChem-Substance/85147464