Macroautophagy in lymphatic endothelial cells inhibits T cell-mediated autoimmunity.
Animals
Arthritis
/ immunology
Autoimmunity
/ immunology
Cell Movement
/ immunology
Cells, Cultured
Endothelial Cells
/ immunology
Humans
Immune Tolerance
/ immunology
Inflammation
/ immunology
Lymph Nodes
/ immunology
Lymphatic Vessels
/ immunology
Lysophospholipids
/ immunology
Macroautophagy
/ immunology
Mice
Mice, Inbred C57BL
Sphingosine
/ analogs & derivatives
T-Lymphocytes, Regulatory
/ immunology
Th17 Cells
/ immunology
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
07 06 2021
07 06 2021
Historique:
received:
18
08
2020
revised:
21
12
2020
accepted:
05
02
2021
entrez:
16
4
2021
pubmed:
17
4
2021
medline:
2
10
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33861848
pii: 212000
doi: 10.1084/jem.20201776
pmc: PMC8056750
pii:
doi:
Substances chimiques
Lysophospholipids
0
sphingosine 1-phosphate
26993-30-6
Sphingosine
NGZ37HRE42
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021 Harlé et al.
Déclaration de conflit d'intérêts
Disclosures: The authors declare no competing interests exist.
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