Topical 1,25-dihydroxyvitamin D3 subverts the priming ability of draining lymph node dendritic cells

P>The active form of vitamin D, 1,25-hydroxyvitamin D-3 [1,25(OH)(2)D-3] is produced in skin following exposure to sunlight. It is also used topically to control inflammatory skin diseases by stimulating keratinocyte differentiation and suppressing immune responses. Administration of 1,25(OH)(2)D-3 to the skin of mice increases the capacity of CD4+ CD25+ (Foxp3+) regulatory T cells residing in the skin-draining lymph nodes (SDLN) to suppress immune responses. We hypothesized that dendritic cells (DC) may migrate from the skin to the lymph nodes to regulate T-cell function. Increased proportions of skin-derived DC (CD11c+ ClassII+ DEC-205hi CD8lo) cells were detected in the SDLN 18 hr after topical 1,25(OH)(2)D-3 treatment of mouse skin. The capacity of DC from the SDLN to take up, process and present antigen to co-cultured T cells was not modified following topical 1,25(OH)(2)D-3. However, CD11c+ cells from the SDLN of 1,25(OH)(2)D-3-treated mice induced a significantly smaller ear-swelling response in a T helper type 1/17-mediated model of contact hypersensitivity. CD4+ CD25+ cells isolated from the ear-draining lymph nodes (EDLN) of mice that received ear injections of CD11c+ cells from donor mice topically treated with 1,25(OH)(2)D-3 more potently suppressed effector cell proliferation. In addition, EDLN cells from recipients of CD11c+ cells from 1,25(OH)(2)D-3-treated mice produced increased interleukin-4 levels. The CD11c+ cells from the SDLN of mice treated with topical 1,25(OH)(2)D-3 expressed increased levels of indoleamine 2,3-dioxygenase messenger RNA, a molecule by which topical 1,25(OH)(2)D-3 may enhance the ability of DC to control the suppressive function of CD4+ CD25+ cells.