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1,24-Dihydroxyvitamin D₃ (tacalcitol) prevents skin T-cell infiltration.
- Source :
-
The British journal of dermatology [Br J Dermatol] 2010 Jun; Vol. 162 (6), pp. 1206-15. Date of Electronic Publication: 2010 Feb 15. - Publication Year :
- 2010
-
Abstract
- Background: 1,24-Dihydroxyvitamin D₃ (tacalcitol), a vitamin D(3) compound, has been used to treat T cell-mediated inflammatory skin diseases such as psoriasis, prurigo and vitiligo. The best-known mechanism of action of this compound is inhibition of the abnormal proliferation of keratinocytes and subsequent maturation; however, its effects on skin T-cell recruitment have not yet been evaluated. Cutaneous lymphocyte-associated antigen (CLA), a surface glycoprotein expressed on T cells, plays a critical role in skin T-cell infiltration. We recently reported that 1,25-dihydroxyvitamin D₃ inhibits skin infiltration of CD4+ T cells by suppressing CLA expression on T cells.<br />Objectives: In this study, we investigated the effect of tacalcitol on CLA epitope decoration and on the levels of gut or lymph node homing receptor expression in human T cells.<br />Methods: We cultured human T cells with tacalcitol and analysed the effect on CLA expression and skin-homing ability, and evaluated glycosyltransferase mRNAs. We also performed an in vivo study using an antigen-dependent delayed-type hypersensitivity (DTH) mouse model and investigated the effect of tacalcitol on skin-infiltrating CD4+ T cells.<br />Results: Tacalcitol downregulated the expression of CLA and, in parallel, the E- and P-selectin ligand function; however, it exerted no effect on other homing receptors. Subcutaneously and intraperitoneally administered tacalcitol downregulated skin infiltration of effector CD4+ T cells in an in vivo DTH mouse model.<br />Conclusions: These findings suggest that tacalcitol reduces skin inflammation by partially downregulating CLA expression levels.<br /> (© 2010 The Authors. Journal Compilation © 2010 British Association of Dermatologists.)
- Subjects :
- Adult
Animals
Antigens, Differentiation, T-Lymphocyte metabolism
Dermatitis, Contact immunology
Dermatitis, Contact pathology
Disease Models, Animal
Down-Regulation
E-Selectin metabolism
Female
Flow Cytometry
Humans
Immunohistochemistry
Male
Membrane Glycoproteins metabolism
Mice
P-Selectin metabolism
Receptors, Lymphocyte Homing drug effects
Receptors, Lymphocyte Homing metabolism
T-Lymphocytes metabolism
Antigens, Differentiation, T-Lymphocyte drug effects
Cell Movement drug effects
Dermatologic Agents pharmacology
Dihydroxycholecalciferols pharmacology
Membrane Glycoproteins drug effects
Skin immunology
T-Lymphocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2133
- Volume :
- 162
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The British journal of dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 20163421
- Full Text :
- https://doi.org/10.1111/j.1365-2133.2010.09692.x