Vitamin D3 targets epidermal and dermal dendritic cells for induction of distinct regulatory T cells.

Autor: van der Aar AM; Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands., Sibiryak DS, Bakdash G, van Capel TM, van der Kleij HP, Opstelten DJ, Teunissen MB, Kapsenberg ML, de Jong EC
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2011 Jun; Vol. 127 (6), pp. 1532-40.e7. Date of Electronic Publication: 2011 Apr 17.
DOI: 10.1016/j.jaci.2011.01.068
Abstrakt: Background: The vitamin D metabolite 1,25(OH)2D3 (VitD3) is a potent immunosuppressive drug and, among others, is used for topical treatment of psoriasis. A proposed mechanism of VitD3-mediated suppression is priming of dendritic cells (DCs) to induce regulatory T (Treg) cells.
Objective: Currently, there is confusion about the phenotype of VitD3-induced Treg cells and the DC-derived molecules driving their development. We investigated Treg cell induction after VitD3 priming of 2 distinct skin DC subsets: Langerhans cells (LCs) and dermal dendritic cells (DDCs).
Methods: LCs and DDCs primed with VitD3 were cocultured with allogeneic naive T cells. The phenotype and function of the DCs and induced T cells were analyzed.
Results: Both VitD3-primed DC subtypes induced T cells with regulatory activity. Unexpectedly, whereas the Treg cell populations generated by VitD3-primed LCs were CD25(hi)CD127(lo) forkhead box protein 3 (Foxp3)-positive cells, which meet the criteria of classical inducible Treg cells, the T cells developing in response to VitD3-primed DDCs were Foxp3(-) T(R)1 cells expressing IL-10. Inhibition experiments revealed that LC-derived TGF-β is a key factor in the induction of Foxp3(+) Treg cells, whereas DDC-derived IL-10 is important for the induction of IL-10(+) T(R)1 cells.
Conclusion: Thus we report the novel finding that distinct but closely related DC subsets are differentially programmed by VitD3 to support development of either TGF-β-dependent Foxp3(+) Treg cells or IL-10-dependent IL-10(+) Treg cells.
(Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)
Databáze: MEDLINE
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