Vitamin D deficiency and the pathogenesis of Crohn's disease

J Steroid Biochem Mol Biol. 2018 Jan;175:23-28. doi: 10.1016/j.jsbmb.2016.12.015. Epub 2016 Dec 23.

Abstract

Vitamin D has emerged as a key regulator of innate immune responses to pathogen threat. The hormonal form of vitamin D signals through a nuclear receptor transcription factor and regulates gene transcription. Several papers have shown that vitamin D signaling is active both upstream and downstream of pattern recognition receptors, vanguards of innate immune responses. Crohn's disease (CD) is a relapsing-recurring inflammatory bowel disease (IBD) that arises from dysregulated intestinal innate immunity. Indeed, genetic studies have identified several CD susceptibility markers linked to mechanisms of innate immune responses to infection. Interest in links between vitamin D deficiency and CD has grown substantially, particularly in the last five years. While a number of studies have consistently revealed an association between CD and vitamin D deficiency, recent experimental work has uncovered a compelling mechanistic basis for the contribution of vitamin D deficiency to the pathogenesis of the disease. Moreover, a number of intervention trials have provided generally solid evidence that robust vitamin D supplementation may be of therapeutic benefit to patients with CD. This review summarizes these laboratory and clinical findings.

Keywords: 1α,25-dihydroxyvitamin D(3); Autophagy; Crohn’s disease; Innate immunity; Intervention trials; Vitamin D deficiency; Vitamin D receptor.

Publication types

  • Review

MeSH terms

  • Clinical Trials as Topic
  • Crohn Disease / complications*
  • Crohn Disease / diet therapy
  • Crohn Disease / genetics
  • Crohn Disease / immunology
  • Dietary Supplements
  • Gene Expression Regulation
  • Humans
  • Immunity, Innate / drug effects
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology
  • Nod2 Signaling Adaptor Protein / genetics
  • Nod2 Signaling Adaptor Protein / immunology*
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / immunology*
  • Signal Transduction
  • Transcription, Genetic
  • Vitamin D / analogs & derivatives
  • Vitamin D / immunology*
  • Vitamin D / metabolism
  • Vitamin D / therapeutic use
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / diet therapy
  • Vitamin D Deficiency / genetics
  • Vitamin D Deficiency / immunology
  • Vitamin D Response Element / genetics
  • Vitamin D Response Element / immunology

Substances

  • IL1B protein, human
  • Interleukin-1beta
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Receptors, Calcitriol
  • VDR protein, human
  • Vitamin D
  • 1,25-dihydroxyvitamin D