Macroautophagy in Dendritic Cells Controls the Homeostasis and Stability of Regulatory T Cells.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_C2E4C1B6EC0D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Macroautophagy in Dendritic Cells Controls the Homeostasis and Stability of Regulatory T Cells.
Journal
Cell reports
Author(s)
Niven J., Madelon N., Page N., Caruso A., Harlé G., Lemeille S., Seemayer C.A., Hugues S., Gannagé M.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
02/07/2019
Peer-reviewed
Oui
Volume
28
Number
1
Pages
21-29.e6
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Regulatory T cells (Tregs) play a crucial role in controlling autoimmune and inflammatory responses. Recent studies have demonstrated that dendritic cells (DCs) contribute to the homeostasis of peripheral Tregs. Autophagy, a critical pathway for cellular homeostasis, is active in DCs and is upregulated in different inflammatory conditions. We have shown that Tregs are expanded and have phenotypic alterations and impaired suppressive functions in mice with autophagy-deficient DCs. RNA profiling of Tregs revealed that autophagy in DCs is required to stabilize Treg expression signatures. This phenotype is linked to the downregulation of ICOS-Ligand expression in autophagy-deficient DCs, a consequence of the accumulation of ADAM10, the metalloproteinase responsible for its cleavage. Upon inflammation, in antigen-induced arthritis, mice with autophagy-deficient DCs exhibit increased synovial inflammation and cartilage and bone erosion correlating with Treg-to-Th17 conversion. Our data reveal a mechanism that couples autophagy deficiency in DCs to the function, homeostasis, and stability of Tregs.
Keywords
ADAM10, Autophagy, CD4, ICOS-Ligand, Th17, arthritis, autoimmunity, regulatory T cells
Pubmed
Web of science
Open Access
Yes
Create date
18/07/2019 17:03
Last modification date
21/08/2019 7:10
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