N-acetyltransferase 10 is implicated in the pathogenesis of cycling T cell-mediated autoimmune and inflammatory disorders in mice.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
11
01
2024
accepted:
04
10
2024
medline:
31
10
2024
pubmed:
31
10
2024
entrez:
31
10
2024
Statut:
epublish
Résumé
T cell expansion has a crucial function in both autoimmune and chronic inflammatory diseases, with cycling T cells contributing to the pathogenesis of autoimmune diseases by causing uncontrolled immune responses and tissue damage. Yet the regulatory mechanisms governing T cell expansion remain incompletely understood. Here we show that the enzyme N-acetyltransferase 10 (NAT10) regulates T cell activation and proliferation upon antigen stimulation. T cell-specific NAT10 deficiency in mice reduces the number of mature T cells in peripheral lymphoid organs. Mechanistically, NAT10 acetylates RACK1 at K185, preventing subsequent RACK1 K48-linked ubiquitination and degradation. The increased RACK1 stability alters ribosome formation and cellular metabolism, leading to enhanced supply of energy and biosynthetic precursors and, eventually, T cell proliferation. Our findings thus highlight the essential function of NAT10 in T cell self-renewal and metabolism and elucidate NAT10 mode of action for the potential development of novel therapies for immune-related disorders.
Identifiants
pubmed: 39477944
doi: 10.1038/s41467-024-53350-x
pii: 10.1038/s41467-024-53350-x
doi:
Substances chimiques
N-Terminal Acetyltransferase E
EC 2.3.1.258
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9388Subventions
Organisme : China National Funds for Distinguished Young Scientists
ID : 82125016
Organisme : Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)
ID : LHDMD22H100002
Informations de copyright
© 2024. The Author(s).
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