. 2012 Dec; 131(1):14-22.
doi: 10.1016/j.jaci.2012.10.058.

Can we produce true tolerance in patients with food allergy?

M Cecilia Berin 1 Lloyd Mayer  
  • PMID: 23265693
  •     105 References
  •     22 citations


Immune tolerance is defined as nonresponsiveness of the adaptive immune system to antigens. Immune mechanisms preventing inappropriate immune reactivity to innocuous antigens include deletion of reactive lymphocytes and generation of regulatory T (Treg) cells. The normal response to food antigens is the generation of antigen-specific Treg cells. In patients with food allergy, the dominant immune response is a T(H)2-skewed T-cell response and the generation of food-specific IgE antibodies from B cells. It is not known whether a failure of the Treg cell response is behind this inappropriate immune response, but interventions that boost the Treg cell response, such as mucosal immunotherapy, might lead to a restoration of immune tolerance to foods. Tolerance has been notoriously difficult to restore in animal disease models, but limited data from human trials suggest that tolerance (sustained nonresponsiveness) can be re-established in a subset of patients. Furthermore, studies on the natural history of food allergy indicate that spontaneous development of tolerance to foods over time is not uncommon. The current challenge is to understand the mechanisms responsible for restoration of natural or induced tolerance so that interventions can be developed to more successfully induce tolerance in the majority of patients with food allergy.

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Curr Allergy Asthma Rep, 2015 Jul 04; 15(5). PMID: 26139331    Free PMC article.
Engineering the Microbiome: a Novel Approach to Immunotherapy for Allergic and Immune Diseases.
Nan Shen, Jose C Clemente.
Curr Allergy Asthma Rep, 2015 Jul 06; 15(7). PMID: 26143390
Update on Early Nutrition and Food Allergy in Children.
Sun Eun Lee, Hyeyoung Kim.
Yonsei Med J, 2016 Mar 22; 57(3). PMID: 26996550    Free PMC article.
Epicutaneous immunotherapy induces gastrointestinal LAP+ regulatory T cells and prevents food-induced anaphylaxis.
Leticia Tordesillas, Lucie Mondoulet, +3 authors, M Cecilia Berin.
J Allergy Clin Immunol, 2016 Jul 16; 139(1). PMID: 27417020    Free PMC article.
Deciphering the black box of food allergy mechanisms.
Vanitha Sampath, Dana Tupa, +3 authors, Kari C Nadeau.
Ann Allergy Asthma Immunol, 2016 Dec 23; 118(1). PMID: 28007085    Free PMC article.
Probiotics enhance the effect of allergy immunotherapy on regulating antigen specific B cell activity in asthma patients.
Jun Liu, Feng-Hong Chen, +10 authors, Ping-Chang Yang.
Am J Transl Res, 2017 Jan 13; 8(12). PMID: 28078000    Free PMC article.
Forkhead box protein 3 demethylation is associated with tolerance induction in peanut-induced intestinal allergy.
Meiqin Wang, Ivana V Yang, +4 authors, Erwin W Gelfand.
J Allergy Clin Immunol, 2017 May 10; 141(2). PMID: 28479331    Free PMC article.
The efficacy of oral and subcutaneous antigen-specific immunotherapy in murine cow's milk- and peanut allergy models.
Marlotte M Vonk, Laura Wagenaar, +5 authors, Johan Garssen.
Clin Transl Allergy, 2017 Oct 13; 7. PMID: 29021893    Free PMC article.
Oral Tolerance Development and Maintenance.
Erik Wambre, David Jeong.
Immunol Allergy Clin North Am, 2017 Nov 15; 38(1). PMID: 29132672    Free PMC article.
Oral immunotherapy with omalizumab reverses the Th2 cell-like programme of regulatory T cells and restores their function.
A Abdel-Gadir, L Schneider, +6 authors, T A Chatila.
Clin Exp Allergy, 2018 Apr 28; 48(7). PMID: 29700872    Free PMC article.
Histamine-Releasing Factor, a New Therapeutic Target in Allergic Diseases.
Yu Kawakami, Kazumi Kasakura, Toshiaki Kawakami.
Cells, 2019 Nov 30; 8(12). PMID: 31779161    Free PMC article.
New Perspectives in Food Allergy.
Massimo De Martinis, Maria Maddalena Sirufo, Mariano Suppa, Lia Ginaldi.
Int J Mol Sci, 2020 Feb 27; 21(4). PMID: 32098244    Free PMC article.
Evolution of Immune Responses in Food Immunotherapy.
Johanna M Smeekens, Michael D Kulis.
Immunol Allergy Clin North Am, 2019 Nov 26; 40(1). PMID: 31761123    Free PMC article.
Combined Effects of Lactobacillus rhamnosus and Egg Oral Immunotherapy in a Mouse Model of Egg Allergy.
Byeong Gon Kim, Ji Na Kim, An Soo Jang, Meeyong Shin.
Allergy Asthma Immunol Res, 2020 May 14; 12(4). PMID: 32400134    Free PMC article.
Immunotherapy of Food Allergy: a Comprehensive Review.
Christine Y Y Wai, Nicki Y H Leung, Patrick S C Leung, Ka Hou Chu.
Clin Rev Allergy Immunol, 2017 Sep 21; 57(1). PMID: 28929421
Comparative Analysis of the Microbiome across the Gut-Skin Axis in Atopic Dermatitis.
Dong Hoon Park, Joo Wan Kim, Hi-Joon Park, Dae-Hyun Hahm.
Int J Mol Sci, 2021 May 01; 22(8). PMID: 33921772    Free PMC article.
Masked Delivery of Allergen in Nanoparticles Safely Attenuates Anaphylactic Response in Murine Models of Peanut Allergy.
Kevin R Hughes, Michael N Saunders, +7 authors, Jessica J O'Konek.
Front Allergy, 2022 Apr 08; 3. PMID: 35386645    Free PMC article.