Can we produce true tolerance in patients with food allergy?

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Presentation transcript:

Can we produce true tolerance in patients with food allergy? M. Cecilia Berin, PhD, Lloyd Mayer, MD Journal of Allergy and Clinical Immunology Volume 131, Issue 1, Pages 14-22 (January 2013) DOI: 10.1016/j.jaci.2012.10.058 Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Tolerance and sensitization in the gastrointestinal tract. Under homeostatic conditions, antigens are acquired in the lamina propria and presented in the mesenteric lymph node (MLN) by CD103+ DCs. Through mechanisms involving retinoic acid (RA), TGF-β, indoleamine 2,3-dioxygenase (IDO), and 4-1BB, DCs induce the production of gut-homing iTreg cells and IgA-producing plasma cells. Dietary factors (vitamin A) and microbial factors (Clostridium species and Bacteroides fragilis polysaccharide A [PSA]) promote the generation of Treg cells. Under sensitizing conditions that are induced in mice with adjuvants, TH2 cells are generated through mechanisms that involve OX40 ligand (OX40L), and IgE production is induced. Treg cells actively suppress allergic sensitization to foods. These mechanisms have been described in the naive state; it remains to be determined how antigen delivered as OIT in a sensitized subject would be presented by gastrointestinal DCs and how that would modify the adaptive immune response. Journal of Allergy and Clinical Immunology 2013 131, 14-22DOI: (10.1016/j.jaci.2012.10.058) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Approaches to maximize the safety and efficacy of immunotherapy with food allergens. Immunotherapy with native antigen results in side effects caused by activation of allergic effector cells and a modification of the adaptive T-cell response to enhance Treg cells and suppress TH2 cells. Approaches to increase safety by reducing the activation of allergic effector cells includes using peptides that cannot cross-link IgE, modifying the allergens (by heating or mannosylation), binding to particles like syngeneic leukocytes, and encapsulating in nanoparticles or within microbial carriers. Approaches to boost the immunomodulatory effects on the adaptive immune response include modifying the antigen to provide adjuvants that act on antigen-presenting cells (mannosylation and Toll-like receptor ligands), binding to syngeneic leukocytes (providing tolerogenic cues), or encapsulating the antigen together with microbial adjuvants. Studies are needed to test the effect of adding novel immunomodulatory agents (tolerogenic adjuvants or neutralizing antibodies that target antigen presenting cells) to immunotherapy protocols. Journal of Allergy and Clinical Immunology 2013 131, 14-22DOI: (10.1016/j.jaci.2012.10.058) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions