Vitamins A and D are potent inhibitors of cutaneous lymphocyte-associated antigen expression.
BACKGROUND
Cutaneous lymphocyte-associated antigen (CLA) is a surface glycoprotein expressed by skin-homing T cells. This carbohydrate moiety expressed on mucin-like surface glycoproteins, including P-selectin glycoprotein ligand 1 and CD43, confers binding activity to dermal endothelial E-selectin and is critical for T-cell recruitment to the skin. Vitamin A (retinoic acid [RA]) and the active form of vitamin D3 (1,25 dihydroxyvitamin D3 [1,25D(3)]) have been used to treat certain T cell-mediated inflammatory skin diseases, as well as cutaneous T-cell lymphomas; however, their effect on CLA expression has not been studied.


OBJECTIVE
We analyzed the effects of RA and 1,25D(3) on expression of CLA and other lymphocyte-homing receptors on human T cells.


METHODS
We cultured human T cells with 1,25D(3) and RA and analyzed the expression of CLA and other homing receptors. We also pretreated mice with either vitamin and then induced an antigen-dependent contact hypersensitivity response.


RESULTS
Both RA and 1,25D(3) downregulated expression of the CLA and, in parallel, functional E-selectin ligand. Whereas RA increased expression of the gut-homing receptor alpha4beta7 and reduced L-selectin expression, 1,25D(3) had no effect on other homing receptors. In an in vivo assay treatment with RA or 1,25D(3) downregulated the skin infiltration of effector CD4+ T cells.


CONCLUSIONS
These findings suggest that 1,25D(3) can selectively downregulate CLA expression without influencing lymphocyte migration patterns to other tissues.
Yamanaka
Kei-ichi
K
Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Dimitroff
Charles J
CJ
Fuhlbrigge
Robert C
RC
Kakeda
Masato
M
Kurokawa
Ichiro
I
Mizutani
Hitoshi
H
Kupper
Thomas S
TS
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000008:administration & dosage / Q000494:pharmacology*; D003877:Dermatitis, Contact / Q000188:drug therapy / Q000276:immunology; D015536:Down-Regulation; D019040:E-Selectin / Q000378:metabolism; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014801:Vitamin A / Q000008:administration & dosage / Q000494:pharmacology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D019040:E-Selectin; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing; D014801:Vitamin A; D002762:Cholecalciferol