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a Division of Endocrinology, Diabetes and Metabolism, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA b Department of Microbiology, Immunology, and Molecular Genetics, University of California at Los Angeles, Los Angeles, California, USA c Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA
Key Words: vitamin D • innate immunity • adaptive immunity • macrophage • dendritic cell • tuberculosis
Address for correspondence: Dr. John S. Adams, Division of Endocrinology, Diabetes and Metabolism, Burns and Allen Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Room B-131, Los Angeles, CA 90048, USA. Voice: 310-423-8970; fax: 310-423-4550. adamsj{at}cshs.org
Defensin is a generic name reserved for an endogenously synthesized antimicrobial agent. The purpose of this review is to describe a series of discoveries that led to the proposal that 25-hydroxylated metabolites of vitamin D are key, intracellular regulators of the synthesis and action of naturally occurring defensin molecules against bacterial antigens. The discussion will (1) highlight the basic elements of human immune response that is responsive to vitamin D, (2) recount work relevant to the extrarenal expression of the vitamin D-1-hydroxlase (CYP27b1) in the macrophage as an initiator of the innate immune response, and (3) describe recent work on the relevance of the vitamin D intracrine–autocrine–paracrine system in a model of a common and devastating human disease, tuberculosis.
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