Smith-specific regulatory T cells halt the progression of lupus nephritis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 Feb 2024
06 Feb 2024
Historique:
received:
12
03
2023
accepted:
12
01
2024
medline:
7
2
2024
pubmed:
7
2
2024
entrez:
6
2
2024
Statut:
epublish
Résumé
Antigen-specific regulatory T cells (Tregs) suppress pathogenic autoreactivity and are potential therapeutic candidates for autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus nephritis is associated with autoreactivity to the Smith (Sm) autoantigen and the human leucocyte antigen (HLA)-DR15 haplotype; hence, we investigated the potential of Sm-specific Tregs (Sm-Tregs) to suppress disease. Here we identify a HLA-DR15 restricted immunodominant Sm T cell epitope using biophysical affinity binding assays, then identify high-affinity Sm-specific T cell receptors (TCRs) using high-throughput single-cell sequencing. Using lentiviral vectors, we transduce our lead Sm-specific TCR into Tregs derived from patients with SLE who are anti-Sm and HLA-DR15 positive. Compared with polyclonal mock-transduced Tregs, Sm-Tregs potently suppress Sm-specific pro-inflammatory responses in vitro and suppress disease progression in a humanized mouse model of lupus nephritis. These results show that Sm-Tregs are a promising therapy for SLE.
Identifiants
pubmed: 38321013
doi: 10.1038/s41467-024-45056-x
pii: 10.1038/s41467-024-45056-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
899Subventions
Organisme : Lupus Research Alliance (Lupus Research Alliance, Inc.)
ID : 100012051, 588087 and 850279
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 501100000925, 2017877
Organisme : Amgen (Amgen Inc.)
ID : 100002429, 2021026213-001
Organisme : U.S. Department of Defense (United States Department of Defense)
ID : 100000005, LR210065
Informations de copyright
© 2024. The Author(s).
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