BATF represses BIM to sustain tolerant T cells in the periphery.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
04 12 2023
04 12 2023
Historique:
received:
30
01
2023
revised:
13
08
2023
accepted:
05
10
2023
pmc-release:
20
04
2024
medline:
31
10
2023
pubmed:
20
10
2023
entrez:
20
10
2023
Statut:
ppublish
Résumé
T cells that encounter self-antigens after exiting the thymus avert autoimmunity through peripheral tolerance. Pathways for this include an unresponsive state known as anergy, clonal deletion, and T regulatory (Treg) cell induction. The transcription factor cues and kinetics that guide distinct peripheral tolerance outcomes remain unclear. Here, we found that anergic T cells are epigenetically primed for regulation by the non-classical AP-1 family member BATF. Tolerized BATF-deficient CD4+ T cells were resistant to anergy induction and instead underwent clonal deletion due to proapoptotic BIM (Bcl2l11) upregulation. During prolonged antigen exposure, BIM derepression resulted in fewer PD-1+ conventional T cells as well as loss of peripherally induced FOXP3+ Treg cells. Simultaneous Batf and Bcl2l11 knockdown meanwhile restored anergic T cell survival and Treg cell maintenance. The data identify the AP-1 nuclear factor BATF as a dominant driver of sustained T cell anergy and illustrate a mechanism for divergent peripheral tolerance fates.
Identifiants
pubmed: 37862030
pii: 276348
doi: 10.1084/jem.20230183
pmc: PMC10588758
pii:
doi:
Substances chimiques
Transcription Factor AP-1
0
Bcl-2-Like Protein 11
0
Autoantigens
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : P01 AI035296
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007313
Pays : United States
Informations de copyright
© 2023 Titcombe et al.
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