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Updated: Oct 6, 2025

Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Vitamin D receptor, STAT3, and TET2 cooperate to establish tolerogenesis
Francesc Català-Moll1, Anna G Ferreté-Bonastre1, Gerard Godoy-Tena1
1Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC), Badalona, 08916 Barcelona, Spain.
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.
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