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Keywords:

  • contact hypersensitivity;
  • dendritic cells;
  • skin;
  • tolerance;
  • vitamin D

Summary

The active form of vitamin D, 1,25-hydroxyvitamin D3 [1,25(OH)2D3] 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)2D3 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)2D3 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)2D3. However, CD11c+ cells from the SDLN of 1,25(OH)2D3-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)2D3 more potently suppressed effector cell proliferation. In addition, EDLN cells from recipients of CD11c+ cells from 1,25(OH)2D3-treated mice produced increased interleukin-4 levels. The CD11c+ cells from the SDLN of mice treated with topical 1,25(OH)2D3 expressed increased levels of indoleamine 2,3-dioxygenase messenger RNA, a molecule by which topical 1,25(OH)2D3 may enhance the ability of DC to control the suppressive function of CD4+ CD25+ cells.