Metallothioneins negatively regulate IL-27-induced type 1 regulatory T-cell differentiation.
Details
Serval ID
serval:BIB_DD5D275B55BE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Metallothioneins negatively regulate IL-27-induced type 1 regulatory T-cell differentiation.
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
07/05/2013
Peer-reviewed
Oui
Volume
110
Number
19
Pages
7802-7807
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Publication Status: ppublish
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, T-Lymphocytes, Regulatory/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
21/08/2018 15:59
Last modification date
20/08/2019 16:02