Vitamin D receptor, STAT3, and TET2 cooperate to establish tolerogenesis.
Cell Rep
; 38(3): 110244, 2022 01 18.
Article
in En
| MEDLINE
| ID: mdl-35045292
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dendritic Cells
/
Receptors, Calcitriol
/
Dioxygenases
/
DNA-Binding Proteins
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STAT3 Transcription Factor
/
Immune Tolerance
Limits:
Humans
Language:
En
Journal:
Cell Rep
Year:
2022
Type:
Article
Affiliation country:
Spain