Vitamin D receptor, STAT3, and TET2 cooperate to establish tolerogenesis.
Cell Rep
; 38(3): 110244, 2022 01 18.
Article
en En
| MEDLINE
| ID: mdl-35045292
The active form of vitamin D, 1,25-dihydroxyvitamin D3, induces a stable tolerogenic phenotype in dendritic cells (DCs). This process involves the vitamin D receptor (VDR), which translocates to the nucleus, binds its cognate genomic sites, and promotes epigenetic and transcriptional remodeling. In this study, we report the occurrence of vitamin D-specific DNA demethylation and transcriptional activation at VDR binding sites associated with the acquisition of tolerogenesis in vitro. Differentiation to tolerogenic DCs associates with activation of the IL-6-JAK-STAT3 pathway. We show that JAK2-mediated STAT3 phosphorylation is specific to vitamin D stimulation. VDR and the phosphorylated form of STAT3 interact with each other to form a complex with methylcytosine dioxygenase TET2. Most importantly, pharmacological inhibition of JAK2 reverts vitamin D-induced tolerogenic properties of DCs. This interplay among VDR, STAT3, and TET2 opens up possibilities for modulating DC immunogenic properties in clinics.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Receptores de Calcitriol
/
Dioxigenasas
/
Proteínas de Unión al ADN
/
Factor de Transcripción STAT3
/
Tolerancia Inmunológica
Límite:
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2022
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
Estados Unidos