Mechanisms of immune tolerance relevant to food allergy - 10/08/11

Doi : 10.1016/j.jaci.2010.12.1116

Brian P. Vickery, MD ^a,^⁎ , Amy M. Scurlock, MD ^b, Stacie M. Jones, MD ^b, A. Wesley Burks, MD ^a
^a Division of Pediatric Allergy and Immunology, Duke University School of Medicine, Durham, NC
^b Division of Pediatric Allergy and Immunology, the University of Arkansas for Medical Sciences, Little Rock, Ark

Reprint requests: Brian P. Vickery, MD, DUMC Box 2644, Durham NC 27710.

Abstract

The intestine has an unenviable task: to identify and respond to a constant barrage of environmental stimuli that can be both dangerous and beneficial. The proper execution of this task is central to the homeostasis of the host, and as a result, the gastrointestinal tract contains more lymphocytes than any other tissue compartment in the body, as well as unique antigen-presenting cells with specialized functions. When antigen is initially encountered through the gut, this system generates a robust T cell–mediated hyporesponsiveness called oral tolerance. Although seminal observations of oral tolerance were made a century ago, the relevant mechanisms are only beginning to be unraveled with the use of modern investigational techniques. Food allergy is among the clinical disorders that occur from a failure of this system, and therapies that seek to re-establish tolerance are currently under investigation.

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Key words : Oral tolerance, regulatory T cell, forkhead box protein 3, dendritic cell, food allergy, microbiota, vitamin A, TGF-β, CD103

Abbreviations used : APC, DC, Foxp3, iTreg, MALT, MLN, RA, Treg, TSLP

Plan

Physical factors of dietary antigens

Importance of antigen dose and timing

The microbiome and oral tolerance

Fundamental importance of APCs

T cells: primary effectors of oral tolerance

Bringing oral tolerance induction to the clinic

Conclusions

	Series editors: Joshua A. Boyce, MD, Fred Finkelman, MD, William T. Shearer, MD, PhD, and Donata Vercelli, MD
	Supported by the Food Allergy & Anaphylaxis Network; the Food Allergy Project; the Gerber Foundation; National Institutes of Health (NIH) grant 1 R01-AI06874-01A1, NIH T32 training grant, and NIH grant 1 UL1 RR024128-01 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH); the NIH Roadmap for Medical Research (contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH); the Dorothy & Frank Robins Family; and the National Peanut Board.
	Terms in boldface and italics are defined in the glossary on page 577.