Targeting NF-κB c-Rel in regulatory T cells to treat corneal transplantation rejection.
T cell biology
basic (laboratory) research
corneal transplantation
graft survival
immune modulation
immunosuppression
ophthalmology
rejection
rejection: T cell mediated (TCMR)
science
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
05
07
2021
received:
10
03
2021
accepted:
08
07
2021
pubmed:
14
7
2021
medline:
1
2
2022
entrez:
13
7
2021
Statut:
ppublish
Résumé
The relevance of Tregs in the induction of tolerance against corneal allografts has been well established. Although it is well known that the conversion of Tregs into effector-like cells contributes to the loss of corneal immune privilege, the underlying mechanism is still not fully understood. Using heterologous penetrating keratoplasty model, we found that Tregs from corneal allograft rejected mice (inflam-Tregs) exhibit impaired function and characteristics of effector T cells. Further study showed that the expression of NF-κB c-Rel, a key mediator of effector T cell function, was significantly increased in inflam-Tregs. Mechanistic study revealed that elevated NF-κB c-Rel level in inflam-Tregs impaired Treg function through the promotion of inflammatory cytokine production and glycolysis. More importantly, we demonstrated that targeting NF-κB c-Rel was able to improve the immune suppressive function of inflam-Tregs in vitro and enhance the potential of them to suppress corneal transplantation rejection. Therefore, our current study identified NF-κB c-Rel as a key mediator of the conversion of Tregs into effector-like cells when under inflammatory environment.
Identifiants
pubmed: 34254428
doi: 10.1111/ajt.16760
pii: S1600-6135(22)08834-7
doi:
Substances chimiques
NF-kappa B
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3858-3870Informations de copyright
© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.
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