Allergen-specific IgG antibody signaling through FcγRIIb promotes food tolerance

Burton, Oliver T.; Tamayo, Jaciel M.; Stranks, Amanda J.; Koleoglou, Kyle J.; Oettgen, Hans C.

doi:10.1016/j.jaci.2017.03.045

Cited by 89 publications

(94 citation statements)

References 76 publications

(106 reference statements)

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“…The mechanisms by which the oral preventive regimens induce tolerance to BLG cannot be determined based on our data, but the absence of native BLG-specific IgG1 before i.p. immunisation suggests the exclusion of tolerance mediated by IgG [19]. Rather, the mechanism may involve generating BLG-specific regulatory T cells, as suggested by a previous study using preventive administration of specific peptides derived from BLG [20].…”

Section: Discussionmentioning

confidence: 99%

Preclinical Brown Norway Rat Models for the Assessment of Infant Formulas in the Prevention and Treatment of Cow’s Milk Allergy

Jensen

Larsen

Madsen

et al. 2019

Int Arch Allergy Immunol

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Background: Infant formulas (IFs) based on hydrolysed cow’s milk proteins are central in the management of cow’s milk allergy (CMA) in infants and small children. New IF compositions with improved prevention and treatment properties are needed, along with appropriate preclinical animal models, to evaluate these properties before introduction into humans. Objectives: We aimed to develop preclinical models for the assessment of the primary preventive and desensitising capacity of cow’s milk IF in allergy-prone, high-IgE responder Brown Norway rats. Method: Preventive capacity was assessed in cow’s milk-naïve rats given a 2- or 4-week regimen of whey-based extensively hydrolysed IF (eHF), partially hydrolysed IF (pHF), or intact β-lactoglobulin (BLG) ad libitum in drinking bottles, followed by intraperitoneal (i.p.) immunisation with BLG. Desensitising capacity was assessed in orally BLG-sensitised rats after a 3- or 6-week regimen of eHF, pHF, or intact BLG administration in drinking bottles, followed by i.p. challenge with BLG. Primary preventive and desensitising capacity were analysed by serum BLG-specific IgG1 and IgE. Results: The preventive regimens did not induce detectable BLG-specific IgG1 or IgE in cow’s milk-naïve rats. A preventive regimen consisting of pHF or BLG, but not eHF, induced complete tolerance to BLG, as demonstrated by the absence of BLG-specific IgE following i.p. immunisation. Desensitising regimens had a limited effect on BLG-specific IgG1 or IgE when comparing sensitised rats before and after treatment. Challenge with BLG (i.p.) increased BLG-specific IgE in all treatment regimens except for in the BLG group, suggesting a limited desensitising capacity of IF based on hydrolysates and a need for the presence of intact allergen for desensitisation. Conclusions: The presented models highlight that different mechanisms are at play in the induction of de novo tolerance to cow’s milk proteins and the desensitisation of CMA. Different IF products may be needed for the primary prevention and treatment of CMA.

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Section: Discussionmentioning

confidence: 99%

Preclinical Brown Norway Rat Models for the Assessment of Infant Formulas in the Prevention and Treatment of Cow’s Milk Allergy

Jensen

Larsen

Madsen

et al. 2019

Int Arch Allergy Immunol

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“…This suggests that rFIP-glu participates in the regulation of the phagocytosis of macrophages and the release of inflammatory mediators. Additionally, FcγRIIb has ability to suppress allergic responses (52–55). This possibly is one of the mechanisms of rFIP-glu-mediated anti-allergy.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory activity of Ganoderma lucidum immunomodulatory protein via PI3K/Akt and MAPK signaling pathways in macrophage RAW264.7 cells

Chang

et al. 2018

Preprint

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Ganoderma lucidum, a traditional edible and medicinal fungus, holds an important status in health care systems in China and other Asian countries. Fungal immunomodulatory protein (FIP), one of the active ingredients isolated from G. lucidum, is a class of naturally occurring proteins and possesses potential biological functions. This study was conducted to explore the molecular mechanism of its immunomodulatory potency in immune responses of macrophages. In vitro assays of biological activity indicated that rFIP-glu significantly activated macrophage RAW264.7 cells, and possessed the ability of pro- and anti-inflammation the cells. RNA sequencing analysis showed that macrophage activation involved Toll-like receptors and mitogen-activated protein kinases pathways. Furthermore, qRT-PCR indicated that phosphoinositide 3 kinase inhibitor LY294002 blocked the mRNA levels of MCP-1, MEK1/2 inhibitor U0126 reduced the mRNA levels of TNF-α and MCP-1, and JNK inhibitor SP600125 prevented the up-regulation of iNOS mRNA in the rFIP-glu-induced cells. FIP-glu mediated these inflammatory effects not through a general pathway, instead through a different pathway for different inflammatory mediator. These data indicate the possibility that rFIP-glu has an important immune-regulation function and thus has potential therapeutic uses.

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“…32,33 It remains unclear whether IgG 4 is a mechanism of protection or a measure of exposure. IgG 4 can function as a blocking antibody, can suppress allergic effector cell activation through FcgRIIb, 34 and can facilitate the development of immune tolerance, 35 likely by changing the phenotype of the antigen-presenting cell after IgG-facilitated uptake and presentation. IgG 4 levels were not predictive of clinical outcome in the natural history cohort, suggesting that they might not play a role in natural resolution of food allergy.…”

Section: Mechanistic Insights From Cofar Studiesmentioning

confidence: 99%

The Consortium for Food Allergy Research (CoFAR): The first generation

Sampson

Berin

Plaut

et al. 2019

Journal of Allergy and Clinical Immunology

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The Consortium for Food Allergy Research (CoFAR) was established by the National Institute of Allergy and Infectious Diseases in 2005 as a collaborative research program bringing together centers focused on the study of food allergy. CoFAR was charged with developing studies to better understand the pathogenesis and natural history of food allergy, as well as potential approaches to the treatment of food allergy. In its first iteration an observational study of infants with milk and egg allergy was established, and studies of oral immunotherapy for egg allergy and sublingual immunotherapy for peanut allergy were initiated, as was a phase 1 study of a recombinant peanut protein vaccine. CoFAR was renewed in 2010 for an additional 5-year period during which the initial observational study was continued, a study of eosinophilic esophagitis was initiated, and new therapeutic trials were established to study epicutaneous immunotherapy for peanut allergy and to compare the safety and efficacy of egg oral immunotherapy to the ingestion of baked egg for the treatment of egg allergy. The results of these efforts will be reviewed in this rostrum, with a brief look to the future of CoFAR. (J Allergy Clin Immunol 2019;143:486-93.)

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Allergen-specific IgG antibody signaling through FcγRIIb promotes food tolerance

Abstract: These findings suggest that allergen-specific IgG antibodies can act to induce and sustain immunologic tolerance to foods.

Cited by 89 publications

References 76 publications

Preclinical Brown Norway Rat Models for the Assessment of Infant Formulas in the Prevention and Treatment of Cow’s Milk Allergy

Preclinical Brown Norway Rat Models for the Assessment of Infant Formulas in the Prevention and Treatment of Cow’s Milk Allergy

Immunomodulatory activity of Ganoderma lucidum immunomodulatory protein via PI3K/Akt and MAPK signaling pathways in macrophage RAW264.7 cells

The Consortium for Food Allergy Research (CoFAR): The first generation

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