Molecular and cellular mechanisms of food allergy and food tolerance - 06/04/16

Doi : 10.1016/j.jaci.2016.02.004

R. Sharon Chinthrajah, MD ^a,^b,^e,^{^{∗
These authors contributed equally to this work.}}, Joseph D. Hernandez, MD, PhD ^b,^c,^e,^{^{∗
These authors contributed equally to this work.}}, Scott D. Boyd, MD, PhD ^c,^e, Stephen J. Galli, MD ^c,^d,^e,^{^{‡
These authors contributed equally to this work as co-senior authors.}}, Kari C. Nadeau, MD, PhD ^a,^b,^e,^{^{‡
These authors contributed equally to this work as co-senior authors.},}^⁎
^a Department of Medicine, Stanford University School of Medicine, Stanford, Calif
^b Department of Pediatrics, Stanford University School of Medicine, Stanford, Calif
^c Department of Pathology, Stanford University School of Medicine, Stanford, Calif
^d Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, Calif
^e Sean N. Parker Center for Allergy & Asthma Research, Stanford University School of Medicine, Stanford, Calif

^∗Corresponding author: Kari C. Nadeau, MD, PhD, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Stanford University School of Medicine, 269 Campus Dr, CCSR 3215, MC 5366, Stanford, CA 94305-5101.Division of Pulmonary and Critical Care MedicineDepartment of MedicineSean N. Parker Center for Allergy and Asthma ResearchStanford UniversityStanford University School of Medicine269 Campus DrCCSR 3215MC 5366StanfordCA94305-5101

Abstract

Ingestion of innocuous antigens, including food proteins, normally results in local and systemic immune nonresponsiveness in a process termed oral tolerance. Oral tolerance to food proteins is likely to be intimately linked to mechanisms that are responsible for gastrointestinal tolerance to large numbers of commensal microbes. Here we review our current understanding of the immune mechanisms responsible for oral tolerance and how perturbations in these mechanisms might promote the loss of oral tolerance and development of food allergies. Roles for the commensal microbiome in promoting oral tolerance and the association of intestinal dysbiosis with food allergy are discussed. Growing evidence supports cutaneous sensitization to food antigens as one possible mechanism leading to the failure to develop or loss of oral tolerance. A goal of immunotherapy for food allergies is to induce sustained desensitization or even true long-term oral tolerance to food allergens through mechanisms that might in part overlap with those associated with the development of natural oral tolerance.

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Key words : Food allergy, microbiome, sensitization, desensitization, immunotherapy, tolerance, regulatory T cells, basophils, mast cells, dendritic cells

Abbreviations used : APC, DC, DNFB, EPIT, Foxp3, GALT, GPR, M cell, MLN, OIT, OVA, SCFA, SLIT, Treg

Plan

Antigen uptake, dissemination, and presentation

Oral tolerance

DCs in oral tolerance

Treg cells in oral tolerance

Allergic sensitization: A breakdown in oral tolerance

More than your average food protein: A role for allergens in sensitization

Strange encounters: Food allergen sensitization through skin

The microbiome in tolerance and allergy

Skin microbiota in patients with food allergy

Probiotic therapy

Immunotherapy: Mechanisms of desensitization and long-term tolerance

Early responses to antigen-specific immunotherapy

T-cell responses to antigen-specific immunotherapy

B-cell responses to antigen-specific immunotherapy

Summary

	Series editors: Joshua A. Boyce, MD, Fred Finkelman, MD, and William T. Shearer, MD, PhD
	Supported by the Sean N. Parker Center for Allergy and Asthma Research; National Institutes of Health grants R01 AR067145 (to S.J.G.) and U19AI10420901 (to S.J.G., K.C.N., S.D.B., and R.S.C.); the American Academy of Allergy, Asthma & Immunology Mylan Anaphylaxis Award and Child Health Research Institute/Lucile Packard Foundation for Children's Health awards (to J.D.H.); Stanford CTSA (UL1 TR001085); and the Department of Pathology, Stanford University.
	Disclosure of potential conflict of interest: R. S. Chinthrajah has received a grant from the National Institutes of Health (NIH) and has had studies sponsored by DBV and Aimmune. J. D. Hernandez has received consultancy fees from LEK Consulting and has received grants from the American Academy of Allergy, Asthma & Immunology and the NIH. S. J. Galli has received grants from the NIH and Stanford University. The rest of the authors declare that they have no relevant conflicts of interest.
	Terms in boldface and italics are defined in the glossary on page 985.