Vitamina D e o Sistema Imune
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Vitamin D and the Immune System: New Perspectives on an Old Theme Martin Hewison, PhD HISTORICAL PERSPECTIVE Nonclassic actions of vitamin D were first recognized 30 years ago when receptors for active 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) were detected in various neoplastic cel ls lines. 1,2 Oth er st udies immedia tely follo wi ng this showed that bin din g of 1,25(OH) 2 D 3 to the vitamin D recept or (VDR) promo ted antipro liferat ive and prodiffe r- entiation responses in cancer cells, 3,4 highlighting an entirely new facet of vitamin D action. The spectrum of nonclassic responses to v itamin D was then extended to include actions on cells from the immune system. 5,6 Thi s interaction was fur the r endorsed by the observation that some pat ients with the granulomatous dise ase sarcoidosis present with increased circulating levels of 1,25(OH) 2 D 3 and associated hypercalcemia. 7,8 In these patients the high serum level of 1,25(OH) 2 D 3 is caused by incr eased activi ty of the enzyme 25-hydroxyvitamin D-1 a-hydro oxyla se (1a- hydroxylase). However, in contrast to normal subjects in whom 1 a-hydroxylase is classically localized in the kidney, the increased synthesis of 1,25(OH) 2 D 3 in patients wi th sarcoidosis involves 1a-hy drox ylase activit y in dise ase -associated macro- phages. 9–11 Thus, it was concluded that the immune system had the potential to synthesize 1,25(OH) 2 D 3 and elicit autocrine or paracrine responses from immune cells expressing the VDR. 12 Despite these early advances, the precise nature of the interaction between vitamin D and the immune system remained unresolved for many years. Some pieces of the puzzle were easier to complete than others. For example, it became evident that dys- regulation of 1,25(OH) 2 D 3 was not restricted to sarcoidosis but was a common feature of many granulomatous disorders and some forms of cancer. 13 Likewise, at least in This work was supported by NIH grant RO1AR050626 to M.H. Department of Ort hopaedic Sur ger y , Molecular Biolog y Ins tit ute, David Geffen School of Medicine at UCLA, 615 Charles East Young Drive South, Los Angeles, CA 90095, USA E-mai l addres s: [email protected] KEYWORDS Vitamin D CYP27b1 Toll-like receptor Macrophage Cathelicidin Regulatory T cells Endocrinol Metab Clin N Am 39 (2010) 365–379 doi:10.1016/j.ecl.2010.02.010 endo.theclinics.com 0889-8529/10 /$ – see front matter ª 2010 Elsevier Inc. All right s reserved.
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