Mapping autophagosome contents identifies interleukin-7 receptor-α as a key cargo modulating CD4+ T cell proliferation.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 09 2022
02 09 2022
Historique:
received:
08
12
2021
accepted:
09
08
2022
entrez:
2
9
2022
pubmed:
3
9
2022
medline:
9
9
2022
Statut:
epublish
Résumé
CD4+ T cells are pivotal cells playing roles in the orchestration of humoral and cytotoxic immune responses. It is known that CD4+ T cell proliferation relies on autophagy, but identification of the autophagosomal cargo involved is missing. Here we create a transgenic mouse model, to enable direct mapping of the proteinaceous content of autophagosomes in primary cells by LC3 proximity labelling. Interleukin-7 receptor-α, a cytokine receptor mostly found in naïve and memory T cells, is reproducibly detected in autophagosomes of activated CD4+ T cells. Consistently, CD4+ T cells lacking autophagy show increased interleukin-7 receptor-α surface expression, while no defect in internalisation is observed. Mechanistically, excessive surface interleukin-7 receptor-α sequestrates the common gamma chain, impairing the interleukin-2 receptor assembly and downstream signalling crucial for T cell proliferation. This study shows that key autophagy substrates can be reliably identified in this mouse model and help mechanistically unravel autophagy's contribution to healthy physiology and disease.
Identifiants
pubmed: 36055998
doi: 10.1038/s41467-022-32718-x
pii: 10.1038/s41467-022-32718-x
pmc: PMC9440129
doi:
Substances chimiques
Interleukin-2
0
Interleukin-7
0
Receptors, Interleukin-7
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5174Subventions
Organisme : Wellcome Trust
ID : 103830/Z/14/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 220784/Z/20/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 100262Z/12/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 208750/Z/17/Z
Pays : United Kingdom
Organisme : Versus Arthritis
ID : 22617
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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