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VITAMIN D AND THE IMMUNE SYSTEM
The immune system defends the body from foreign, invading organisms, promoting protective immunity while maintaining tolerance to self. The implications of vitamin D deficiency on the immune system have become clearer in recent years, and in the context of vitamin D deficiency, there seems to be an increased susceptibility to infection and a diathesis, in a genetically susceptible host to autoimmunity.
The classical actions of vitamin D are to promote calcium homeostasis and to promote bone health. Vitamin D enhances absorption of calcium in the small intestine and stimulates osteoclast differentiation and calcium reabsorption of bone. Vitamin D additionally promotes mineralization of the collagen matrix in bone. In humans, vitamin D is obtained from the diet, or it is synthesized in the skin (reviewed in 1 ). As vitamin D is cutaneously produced after exposure to UV B light, its synthesis is influenced by latitude, season, use of sunblock, and skin pigmentation. Melanin absorbs UVB radiation inhibiting the synthesis of vitamin D from 7-dihydrocholesterol. This initial vitamin D compound is inactive, and it is next hydroxylated in the liver to form 25 OH vitamin D3 (25 D). 25 D also is an inactive compound but is the most reliable measurement of an individual's vitamin D status. It is converted in the kidney to the active compound 1,25 dihydroxy vitamin D (1,25 D) or calcidiol by 1-[alpha]-hydroxylase (CYP27B1), an enzyme which is stimulated by PTH. 1,25 D may be further metabolized to the inactive 1,24,25 vitamin D by 24-hydroxylase (CYP24). 1,25 D levels are tightly regulated in a negative feedback loop. 1,25 D both inhibits renal 1-[alpha]-hydroxylase and stimulates the 24-hydroxylase enzymes, thus maintaining circulating levels within limited boundaries and preventing excessive vitamin D activity/signaling.
1,25 D acts on the intestine, where it stimulates calcium reabsorption, and upon bone, where it promotes osteoblast differentiation and matrix calcification. The active hormone exerts its effects on these tissues by binding to the vitamin D receptor (VDR). This complex dimerizes with the retinoid X receptor (RXR), and the 1,25D-VDR-RXR heterodimer translocates to the nucleus where it binds vitamin D responsive elements in the promoter regions of vitamin D responsive genes and induces expression of these vitamin D-responsive genes.
Many tissues other than...