Document Detail


Expansion of antigen-specific regulatory T cells with the topical vitamin d analog calcipotriol.
MedLine Citation:
PMID:  19414758     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Mehran Ghoreishi; Paxton Bach; Jennifer Obst; Mitsuhiro Komba; James C Fleet; Jan P Dutz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  182     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-05     Completed Date:  2009-05-26     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6071-8     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Administration, Topical
Allergens / immunology
Animals
CD8-Positive T-Lymphocytes / drug effects,  immunology,  metabolism
Calcitriol / administration & dosage,  analogs & derivatives*
Dermatologic Agents / administration & dosage*
Flow Cytometry
Immune Tolerance
Immunohistochemistry
Keratinocytes / drug effects,  immunology,  metabolism
Lymphocyte Activation / immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Ovalbumin / immunology
RANK Ligand / drug effects,  metabolism
Receptors, Calcitriol / genetics,  immunology,  metabolism
Skin / drug effects*,  immunology
T-Lymphocytes, Regulatory / drug effects*,  immunology,  metabolism
Ultraviolet Rays
Vitamin D / analogs & derivatives*,  immunology
Grant Support
ID/Acronym/Agency:
R01 DK054111/DK/NIDDK NIH HHS; R01 DK054111-10/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Allergens; 0/Dermatologic Agents; 0/RANK Ligand; 0/Receptors, Calcitriol; 112965-21-6/calcipotriene; 1406-16-2/Vitamin D; 9006-59-1/Ovalbumin; FXC9231JVH/Calcitriol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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