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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0170v1 198/2/261    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chun, R. Articles by Hewison, M. Search for Related Content PubMed PubMed Citation Articles by Chun, R. Articles by Hewison, M.

R Chun, Dept. of Orthopaedic Surgery, UCLA-Orthopaedic Hospital, Los Angeles, United States
J Adams, Dept. of Orthopaedic Surgery, UCLA-Orthopaedic Hospital, Los Angeles, United States
M Hewison, Dept. of Orthopaedic Surgery, UCLA-Orthopaedic Hospital, Los Angeles, CA 90095-7358, United States

Correspondence: Martin Hewison, Email: mhewison{at}mednet.ucla.edu

Abstract

Our perception of the vitamin D system continues to evolve. Recent studies have re-evaluated the parameters for adequate vitamin D status in humans, revealing a high prevalence of insufficiency in many populations throughout the world. Other reports have highlighted the potential consequences of vitamin D insufficiency beyond established effects on bone homeostasis. Most notably there is now strong evidence of a role for vitamin D in modulating innate and adaptive immunity, with insufficiency being linked to infectious disease and other immune disorders. To date, signaling pathways for these new responses to vitamin D have been based on established endocrine models for active 1,25-dihydroxyvitamin D, despite current evidence for more localized, intracrine modes of action. In the following review, we provide a fresh perspective on vitamin D signaling in non-classical target cells such as macrophages by highlighting novel factors associated with the transport and action of this pluripotent seco-steroid.