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
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
Author(s)
Wu C., Pot C., Apetoh L., Thalhamer T., Zhu B., Murugaiyan G., Xiao S., Lee Y., Rangachari M., Yosef N., Kuchroo V.K.
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
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
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