Potential mechanisms for the hypothesized link between sunshine, vitamin D, and food allergy in children
Journal of Allergy and Clinical Immunology
Copyright © 2010 American Academy of Allergy, Asthma & Immunology Published by Mosby, Inc.
Milo F. Vassallo MD, PhDa and Carlos A. Camargo Jr. MD, DrPH, FAAAAIa, b, c, Corresponding Author Contact Information, E-mail The Corresponding Author
a Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass
b Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass
c Department of Epidemiology, Harvard School of Public Health, Boston, Mass
Received 18 February 2010;
revised 14 June 2010;
accepted 15 June 2010.
Available online 10 July 2010.
Epidemiologic data suggest that the incidence of food allergy (FA) is increasing among children, yet a satisfactory model of its pathogenesis remains elusive. FA is the consequence of maladaptive immune responses to common and otherwise innocuous food antigens. Concurrent with the increase in FA is an epidemic of vitamin D deficiency (VDD) caused by several factors, especially decreased sunlight/UVB exposure. There is growing appreciation of the importance of the pleiotropic hormone vitamin D in the development of tolerance, immune system defenses, and epithelial barrier integrity. We propose a “multiple-hit” model in which VDD in a developmentally critical period increases susceptibility to colonization with abnormal intestinal microbial flora and gastrointestinal infections, contributing to abnormal intestinal barrier permeability and excess and inappropriate exposure of the immune system to dietary allergens. A compounding effect (and additional “hit”) of VDD is the promotion of a pro-sensitization immune imbalance that might compromise immunologic tolerance and contribute to FA. We propose that early correction of VDD might promote mucosal immunity, healthy microbial ecology, and allergen tolerance and thereby blunt the FA epidemic in children.
Vitamin D deficiency
The vitamin D–FA hypothesis
Vitamin D, the immune system, and tolerance
Vitamin D, microbes, and barrier function
Microbes in the pathogenesis of FA
The importance of timing
Evaluation of the hypothesis
Predictions and weaknesses of the hypothesis
Fig 1. A model for the pathogenesis of childhood FA. VDD contributes to immune system defects, abnormal microbial flora, gastrointestinal infections, and compromised mucosal barrier integrity. DC, Dendritic cell; MHCII, major histocompatibility complex II molecule.
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