Mechanisms Underlying the Regulation of Innate and Adaptive Immunity by Vitamin D.

Ran Wei,Sylvia Christakos

doi:10.3390/nu7105392

Ran Wei, Sylvia Christakos

Open Access

https://doi.org/10.3390/nu7105392

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Journal: Nutrients	Publication Date: Sep 24, 2015
Citations: 285	License type: CC BY 4.0

Affiliation: Rutgers, The State University of New Jersey

Abstract

Non-classical actions of vitamin D were first suggested over 30 years ago when receptors for the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), were detected in various tissues and cells that are not associated with the regulation of calcium homeostasis, including activated human inflammatory cells. The question that remained was the biological significance of the presence of vitamin D receptors in the different tissues and cells and, with regard to the immune system, whether or not vitamin D plays a role in the normal immune response and in modifying immune mediated diseases. In this article findings indicating that vitamin D is a key factor regulating both innate and adaptive immunity are reviewed with a focus on the molecular mechanisms involved. In addition, the physiological significance of vitamin D action, as suggested by in vivo studies in mouse models is discussed. Together, the findings indicate the importance of 1,25(OH)2D3 as a regulator of key components of the immune system. An understanding of the mechanisms involved will lead to potential therapeutic applications for the treatment of immune mediated diseases.

Highlights

The importance of vitamin D for curing rickets has been known for over 80 years, in the past several years there has been a renewed interest in vitamin D
In spite of the potential importance of vitamin D over a wide range of immune disorders, the mechanisms involved in vitamin D regulation of immune responses and how vitamin D is involved in linking innate and adaptive immunity have not been clearly defined and are topics of ongoing investigation. 1,25(OH)2D3, the hormonally active form of vitamin D, is produced by two sequential hydroxylations: by 25-hydroxylase in the liver and by 25-hydroxyvitamin D 1α hydroxylase (CYP27B1) in the kidney [1,2,3]
The actions of 1,25(OH)2D3 are mediated, similar to other hormones, by a nuclear receptor which heterodimerizes with the retinoid X receptor and binds to vitamin D response elements (VDREs) in target genes and modulates their transcription [4,5,6]. 1,25(OH)2D3 modulates two separate, but interacting, types of immunity: innate and adaptive

Summary

Introduction

The importance of vitamin D for curing rickets has been known for over 80 years, in the past several years there has been a renewed interest in vitamin D. This is due to an increased awareness of the importance of vitamin D for mineralization and to the realization that vitamin D has many other effects including preventing or, at least partially, protecting against a number of autoimmune diseases (for example, experimental autoimmune encephalomyelitis (EAE; the murine model of multiple sclerosis, MS) and inflammatory bowel disease (IBD). Effects on each system, including molecular mechanisms involved, will be reviewed and in vivo studies in mouse models will be discussed

Effects of Vitamin D on Innate Immunity

Findings

Conclusions