Macroautophagy in lymphatic endothelial cells inhibits T cell-mediated autoimmunity.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_44434EB79885
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Macroautophagy in lymphatic endothelial cells inhibits T cell-mediated autoimmunity.
Journal
The Journal of experimental medicine
Author(s)
Harlé G., Kowalski C., Dubrot J., Brighouse D., Clavel G., Pick R., Bessis N., Niven J., Scheiermann C., Gannagé M. (co-last), Hugues S.
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Publication state
Published
Issued date
07/06/2021
Peer-reviewed
Oui
Volume
218
Number
6
Pages
e20201776
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Lymphatic endothelial cells (LECs) present peripheral tissue antigens to induce T cell tolerance. In addition, LECs are the main source of sphingosine-1-phosphate (S1P), promoting naive T cell survival and effector T cell exit from lymph nodes (LNs). Autophagy is a physiological process essential for cellular homeostasis. We investigated whether autophagy in LECs modulates T cell activation in experimental arthritis. Whereas genetic abrogation of autophagy in LECs does not alter immune homeostasis, it induces alterations of the regulatory T cell (T reg cell) population in LNs from arthritic mice, which might be linked to MHCII-mediated antigen presentation by LECs. Furthermore, inflammation-induced autophagy in LECs promotes the degradation of Sphingosine kinase 1 (SphK1), resulting in decreased S1P production. Consequently, in arthritic mice lacking autophagy in LECs, pathogenic Th17 cell migration toward LEC-derived S1P gradients and egress from LNs are enhanced, as well as infiltration of inflamed joints, resulting in exacerbated arthritis. Our results highlight the autophagy pathway as an important regulator of LEC immunomodulatory functions in inflammatory conditions.
Pubmed
Web of science
Open Access
Yes
Create date
26/04/2021 13:12
Last modification date
04/02/2022 7:34
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