Vitamin D and Inflammation of the Skin

1,24-Dihydroxyvitamin D₃ (tacalcitol) prevents skin T-cell infiltration.
Yamanaka KI, Kakeda M, Kitagawa H, Tsuda K, Akeda T, Kurokawa I, Gabazza EC, Kupper TS, Mizutani H.
Source
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
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.

The new focus, therefore, is the implication of various activators of inflammation in the etiology of androgenetic alopecia. An early study referred to an inflammatory infiltrate of mononuclear cells and lymphocytes in about 50 percent of the scalp samples observed. Jaworsky et al. subsequently in 1992 referred to an inflammatory infiltrate of activated T cells and macrophages in the upper third of the hair follicles, associated with an enlargement of the follicular dermal-sheath composed of collagen bundles (perifollicular fibrosis), in regions of actively progressing alopecia. Whiting has documented that horizontal sections of scalp biopsies indicated that the perifollicular fibrosis is generally mild, consisting of loose, concentric layers of collagen (a fibrous protein that makes up connective tissue) that must be distinguished from cicatricial alopecia. Another study conducted on 412 patients (193men and 219 women) showed the presence of a significant degree of inflammation and fibrosis in at least 37 percent of androgenetic alopecia cases.