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


OBJECTIVE
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.
Yamanaka
K-I
KI
Department of Dermatology Immunology, Mie University, Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. yamake@clin.medic.mie-u.ac.jp
Kakeda
M
M
Kitagawa
H
H
Tsuda
K
K
Akeda
T
T
Kurokawa
I
I
Gabazza
E C
EC
Kupper
T S
TS
Mizutani
H
H
D000328:Adult; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000187:drug effects* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D003877:Dermatitis, Contact / Q000276:immunology / Q000473:pathology; D003879:Dermatologic Agents / Q000494:pharmacology*; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D019007:P-Selectin / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000187:drug effects / Q000378:metabolism; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; C063419:CTAGE1 protein, human; D003879:Dermatologic Agents; D004100:Dihydroxycholecalciferols; D019040:E-Selectin; D008562:Membrane Glycoproteins; D019007:P-Selectin; D016201:Receptors, Lymphocyte Homing; C023850:1 alpha,24-dihydroxyvitamin D3