Vitamin D and the Immune System: New Perspectives on an Old Theme

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Historical perspective

Nonclassic actions of vitamin D were first recognized 30 years ago when receptors for active 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) were detected in various neoplastic cells lines.1, 2 Other studies immediately following this showed that binding of 1,25(OH)2D3 to the vitamin D receptor (VDR) promoted antiproliferative and prodifferentiation responses in cancer cells,3, 4 highlighting an entirely new facet of vitamin D action. The spectrum of nonclassic responses to vitamin D was then extended

Macrophages, Vitamin D, and Cathelicidin

Consistent with the earlier seminal observations of extrarenal 1α-hydroxylase activity in patients with sarcoidosis, the effects of vitamin D on macrophage function have been central to many of the new observations implicating vitamin D in the regulation of immune responses. In common with natural killer cells (NK) and cytotoxic T lymphocytes (cytotoxic T cells), macrophages, and their monocyte precursors play a central role in initial nonspecific immune responses to pathogenic organisms or

Vitamin D and T-cell Function

Resting T cells express almost undetectable levels of VDR, but levels of the receptor increase as T cells proliferate following antigenic activation.48, 49, 50 As a consequence, initial studies of the effects of vitamin D on T cells focused on the ability of 1,25(OH)2D3 to suppress T-cell proliferation.48, 49, 50 However, the recognition that CD4+ effector T cells were capable of considerable phenotypic plasticity, suggested that vitamin D might also influence the phenotype of T cells. Lemire

Vitamin D, the immune system and human health

For many years vitamin D status was defined simply by whether or not the patient had symptoms of the bone disease rickets (osteomalacia in adults). However, an entirely new perspective on vitamin D status has arisen from the observation that serum levels of the main circulating form of vitamin D (25OHD3) as high as 75 nM correlate inversely with parathyroid hormone.81 This, has prompted the introduction of a new term, vitamin D insufficiency, defined by serum levels of 25OHD3 that are

Summary

It is almost 30 years since an interaction between vitamin D and the immune system was first documented. Although this was initially proposed as a nonclassic effect of vitamin D associated with granulomatous diseases, our current view is now changed considerably. Recent studies have shown a potential physiologic role for vitamin D in regulating normal innate and adaptive immunity. Future studies now need to focus on the clinical implications of vitamin D–mediated immunity and, in particular,

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    This work was supported by NIH grant RO1AR050626 to M.H.

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