The AP-1 transcription factors c-Jun and JunB are essential for CD8α conventional dendritic cell identity.


Journal

Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445

Informations de publication

Date de publication:
08 2021
Historique:
received: 28 10 2020
accepted: 24 02 2021
revised: 17 02 2021
pubmed: 25 3 2021
medline: 19 3 2022
entrez: 24 3 2021
Statut: ppublish

Résumé

Dendritic cell (DC) development is orchestrated by lineage-determining transcription factors (TFs). Although, members of the activator-protein-1 (AP-1) family, including Batf3, have been implicated in conventional (c)DC specification, the role of Jun proteins is poorly understood. Here, we identified c-Jun and JunB as essential for cDC1 fate specification and function. In mice, Jun proteins regulate extrinsic and intrinsic pathways, which control CD8α cDC1 diversification, whereas CD103 cDC1 development is unaffected. The loss of c-Jun and JunB in DC progenitors diminishes the CD8α cDC1 pool and thus confers resistance to Listeria monocytogenes infection. Their absence in CD8α cDC1 results in impaired TLR triggering and antigen cross-presentation. Both TFs are required for the maintenance of the CD8α cDC1 subset and suppression of cDC2 identity on a transcriptional and phenotypic level. Taken together, these results demonstrate the essential role of c-Jun and JunB in CD8α cDC1 diversification, function, and maintenance of their identity.

Identifiants

pubmed: 33758366
doi: 10.1038/s41418-021-00765-4
pii: 10.1038/s41418-021-00765-4
pmc: PMC8329169
doi:

Substances chimiques

JunB protein, mouse 0
Transcription Factor AP-1 0
Transcription Factors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2404-2420

Subventions

Organisme : Austrian Science Fund FWF
ID : DOC 32
Pays : Austria

Informations de copyright

© 2021. The Author(s).

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Auteurs

Philipp Novoszel (P)

Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Barbara Drobits (B)

Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Martin Holcmann (M)

Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Cristiano De Sa Fernandes (CS)

Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Roland Tschismarov (R)

Department of Microbiology, Immunobiology and Genetics, Max Perutz Labs, University of Vienna, Vienna, Austria.

Sophia Derdak (S)

Core Facilities, Medical University of Vienna, Vienna, Austria.

Thomas Decker (T)

Department of Microbiology, Immunobiology and Genetics, Max Perutz Labs, University of Vienna, Vienna, Austria.

Erwin F Wagner (EF)

Department of Dermatology and Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.

Maria Sibilia (M)

Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. Maria.Sibilia@meduniwien.ac.at.

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