1,24-Dihydroxyvitamin D₃ (tacalcitol) prevents skin T-cell infiltration.

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.

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.

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.

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.

CONCLUSIONS:

These findings suggest that tacalcitol reduces skin inflammation by partially downregulating CLA expression levels.

• Authors: K-I Yamanaka, M Kakeda, H Kitagawa, K Tsuda, T Akeda, I Kurokawa, E C Gabazza, T S Kupper, H Mizutani
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 162 Issue 6 Pg. 1206-15 (Jun 2010) ISSN: 1365-2133 [Electronic] England
• PMID: 20163421 (Publication Type: Journal Article)
• Copyright: © 2010 The Authors. Journal Compilation © 2010 British Association of Dermatologists.

Chemical References

• Antigens, Differentiation, T-Lymphocyte
• CTAGE1 protein, human
• Dermatologic Agents
• Dihydroxycholecalciferols
• E-Selectin
• Membrane Glycoproteins
• P-Selectin
• Receptors, Lymphocyte Homing
• 1 alpha,24-dihydroxyvitamin D3

Topics

• Adult
• Animals
• Antigens, Differentiation, T-Lymphocyte (drug effects, metabolism)
• Cell Movement (drug effects)
• Dermatitis, Contact (immunology, pathology)
• Dermatologic Agents (pharmacology)
• Dihydroxycholecalciferols (pharmacology)
• Disease Models, Animal
• Down-Regulation
• E-Selectin (metabolism)
• Female
• Flow Cytometry
• Humans
• Immunohistochemistry
• Male
• Membrane Glycoproteins (drug effects, metabolism)
• Mice
• P-Selectin (metabolism)
• Receptors, Lymphocyte Homing (drug effects, metabolism)
• Skin (immunology)
• T-Lymphocytes (drug effects, metabolism)