Interferon-β acts directly on T cells to prolong allograft survival by enhancing regulatory T cell induction through Foxp3 acetylation.
CTLA-4 Ig
Foxp3
acetylation
interferon-beta
regulatory T cells
transplant
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
08 03 2022
08 03 2022
Historique:
received:
29
07
2020
revised:
18
06
2021
accepted:
13
01
2022
pubmed:
13
2
2022
medline:
6
5
2022
entrez:
12
2
2022
Statut:
ppublish
Résumé
Type I interferons (IFNs) are pleiotropic cytokines with potent antiviral properties that also promote protective T cell and humoral immunity. Paradoxically, type I IFNs, including the widely expressed IFNβ, also have immunosuppressive properties, including promoting persistent viral infections and treating T-cell-driven, remitting-relapsing multiple sclerosis. Although associative evidence suggests that IFNβ mediates these immunosuppressive effects by impacting regulatory T (Treg) cells, mechanistic links remain elusive. Here, we found that IFNβ enhanced graft survival in a Treg-cell-dependent murine transplant model. Genetic conditional deletion models revealed that the extended allograft survival was Treg cell-mediated and required IFNβ signaling on T cells. Using an in silico computational model and analysis of human immune cells, we found that IFNβ directly promoted Treg cell induction via STAT1- and P300-dependent Foxp3 acetylation. These findings identify a mechanistic connection between the immunosuppressive effects of IFNβ and Treg cells, with therapeutic implications for transplantation, autoimmunity, and malignancy.
Identifiants
pubmed: 35148827
pii: S1074-7613(22)00040-1
doi: 10.1016/j.immuni.2022.01.011
pmc: PMC8917088
mid: NIHMS1781177
pii:
doi:
Substances chimiques
FOXP3 protein, human
0
Forkhead Transcription Factors
0
Foxp3 protein, mouse
0
Interferon-beta
77238-31-4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
459-474.e7Subventions
Organisme : NIAID NIH HHS
ID : R01 AI141710
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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