Extracellular redox modulation by regulatory T cells.
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.
Yan
Zhonghua
Z
Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Garg
Sanjay K
SK
Kipnis
Jonathan
J
Banerjee
Ruma
R
D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D003545:Cysteine / Q000378:metabolism* / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D005978:Glutathione; D003545:Cysteine