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Expansion of antigen-specific regulatory T cells with the topical vitamin d analog calcipotriol.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2009 May 15; Vol. 182 (10), pp. 6071-8. - Publication Year :
- 2009
-
Abstract
- 1,25-Dihydroxyvitamin D(3) is immunosuppressive both in vivo and in vitro. Topical vitamin D analogs such as calcipotriol alter keratinocyte function, but their effects on cutaneous immune responses are less well understood. We demonstrate that exposure of the skin to calcipotriol before transcutaneous immunization with OVA protein and CpG adjuvant prevents Ag-specific CD8(+) T cell priming coincident with Langerhans cell depletion in the skin. Immunization through calcipotriol-treated skin induces CD4(+)CD25(+) regulatory T cells (Treg) that prevent subsequent Ag-specific CD8(+) T cell proliferation and IFN-gamma production. Treg induced by calcipotriol are able to inhibit the induction and the elicitation of protein contact hypersensitivity. Topical calcipotriol treatment also induces RANKL (receptor activator of NF-kappaB ligand) expression by keratinocytes, a TNF family member involved in modulation of skin dendritic cells. UV light B induces Ag-specific tolerance when it is applied before transcutaneous immunization. We suggest that UV light B-induced tolerance is induced via a vitamin D receptor-dependent mechanism as vitamin D receptor (VDR) knockout mice fail to increase FoxP3(+) Treg in their peripheral draining lymph node following irradiation. Additionally, keratinocytes of VDR(-/-) mice fail to induce RANKL upon UV irradiation or calcipotriol treatment. The in vivo expansion of Ag-specific Treg with the topical application of the vitamin D analog calcipotriol followed by transcutaneous immunization is a simple method to augment functional Ag-specific CD4(+)CD25(+)Foxp3(+) Treg populations and mimics Ag-specific UV-induced tolerance.
- Subjects :
- Administration, Topical
Allergens immunology
Animals
CD8-Positive T-Lymphocytes drug effects
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Calcitriol administration & dosage
Flow Cytometry
Immune Tolerance
Immunohistochemistry
Keratinocytes drug effects
Keratinocytes immunology
Keratinocytes metabolism
Lymphocyte Activation immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Ovalbumin immunology
RANK Ligand drug effects
RANK Ligand metabolism
Receptors, Calcitriol genetics
Receptors, Calcitriol immunology
Receptors, Calcitriol metabolism
Skin immunology
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory metabolism
Ultraviolet Rays
Vitamin D immunology
Calcitriol analogs & derivatives
Dermatologic Agents administration & dosage
Skin drug effects
T-Lymphocytes, Regulatory drug effects
Vitamin D analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 182
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 19414758
- Full Text :
- https://doi.org/10.4049/jimmunol.0804064