Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy

Hussain, Maryam; Borcard, Loïc; Walsh, Kevin; Rodriguez, Maria Pena; Mueller, Christoph; Kim, Brian; Kubo, Masato; Artis, David; Noti, Mario

doi:10.1016/j.jaci.2017.02.035

Cited by 132 publications

(129 citation statements)

References 54 publications

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“…When the sensitized mice were challenged with FSM, the serum mMCP‐1 concentrations decreased compared with those of the SM group, indicating that FSM might alter the activation and function of mast cells. Moreover, as another marker of effector cells, basophils play a key and non‐redundant role in the immune system, representing less than 1% of peripheral blood leukocytes . Histamine is another marker of allergen‐induced cell activation, and the level of histamine can indicate the activation of mast cells and basophils.…”

Section: Resultssupporting

confidence: 89%

Allergenicity reduction and rheology property of Lactobacillus‐fermented soymilk

Xia

Yang

et al. 2019

J Sci Food Agric

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BACKGROUND This study aimed to investigate the reduction in the potential allergenicity of soymilk, and its rheological properties, after fermentation with Lactobacillus. Soymilk (SM) was fermented with Lactobacillus brevis and Lactobacillus sp. The molecular weight of fermented soymilk (FSM) was characterized using sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS‐PAGE), and the potential allergenicity of FSM was analyzed using enzyme‐linked immunosorbent assay in vitro and the BALB/c mouse model to detect changes in histamine, mouse mast cell protease‐1 (mMCP‐1), allergen‐specific IgG/IgE, and cytokine levels and histomorphology of jejunum in vivo. RESULTS The SDS‐PAGE and enzyme linked immunosorbent assay (ELISA) showed that allergens of soybean (β‐conglycinin and acidic subunit of glycinin) were almost degraded, and their immunoreactivity was decreased. In the BALB/c mouse model, the FSM group did not show anaphylactic shock symptoms compared with the SM group. Moreover, a tendency toward decreased serum allergen‐specific IgG/IgE levels, plasma histamine levels, and mMCP‐1 concentrations was observed in the FSM group. Furthermore, Th2‐related cytokines were decreased, while IFN‐γ production increased in spleen cell cultures. The intestinal villus was slightly damaged after the challenge. All these findings indicated that the Th1/Th2 balance in the FSM group shifted toward a Th1 response, ultimately reducing the potential allergenicity of FSM. Rheological assessment suggested that FSM has good viscous and pseudoplastic properties. CONCLUSION Fermentation might be a promising method for producing tasty, hypoallergenic soybean products. © 2019 Society of Chemical Industry

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Section: Resultssupporting

confidence: 89%

Allergenicity reduction and rheology property of Lactobacillus‐fermented soymilk

Xia

Yang

et al. 2019

J Sci Food Agric

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“…Skin administration of a vitamin D analog (MC903) induced epithelial cell‐derived TSLP that initiated basophil activation and accumulation of ILC2s, which contribute to Th2 cytokine‐mediated AD‐like skin lesions . The basophil‐derived IL‐4 was required for the optimal accumulation of ILC2s in the inflamed skin lesions and for epicutaneous sensitization to food antigens in the skin and in food allergy effector responses . Indeed, mice lacking the Il4 3′ UTR fail to develop IgE‐mediated food allergy.…”

Section: Basophil‐derived Il‐4 In Allergic Lung Inflammationmentioning

confidence: 99%

“…They were identified in different laboratories and originally had several designations—innate helper type 2 (Ih2) cells, multipotent progenitor type 2 (MPP type2 ) cells, natural helper cells, and nuocytes—but are now classified as ILC2s . ILC2s produce high levels of IL‐5, IL‐6, and IL‐13 in response to epithelial or myeloid cell‐derived IL‐25, IL‐33, and TSLP after exposure to protease allergens, chemicals, or helminth parasites . These innate lymphocytes have also been found in several other tissues including the liver, spleen, and lung .…”

Section: Ilc2 In Allergic Inflammationmentioning

confidence: 99%

Innate and adaptive type 2 immunity in lung allergic inflammation

Kubo

2017

Immunological Reviews

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233

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Allergic inflammation is a type 2 immune disorder classically characterized by high levels of immunoglobulin E (IgE) and the development of Th2 cells. Asthma is a pulmonary allergic inflammatory disease resulting in bronchial hyper-reactivity. Atopic asthma is defined by IgE antibody-mediated mast cell degranulation, while in non-atopic asthma there is no allergen-specific IgE and more involvement of innate immune cells, such as basophils, group 2 innate lymphoid cells (ILC2), and eosinophils. Recently, protease allergens were shown to cause asthmatic responses in the absence of Th2 cells, suggesting that an innate cell network (IL-33/TSLP-basophil-ILC2-IL-5/IL-13 axis) can facilitate the sensitization phase of type 2 inflammatory responses. Recent evidence also indicates that in the chronic phase, these innate immune cells directly or indirectly contribute to the adaptive Th2 cell responses. In this review, we discuss the role of Th2 cytokines (IL-4 and IL-13) and innate immune cells (mast cells, basophils, ILC2s, and dendritic cells) in the cross-talk between innate and adaptive inflammatory responses.

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“…171,172 Studies investigating the role of TSLP and IL-25 in the context of food allergy are limited, and recent data on the topic are still derived from rodent in vivo and in vitro models. 15,85 Currently, there are trials of biologics targeting TSLP in asthma (NCT02698501), and in combination with cat immunotherapy (NCT02237196), but not food allergies. A therapeutic antibody targeting IL-33 (etokimab) was applied in a clinical trial to treat peanut allergy in adults with some promise (NCT02920021).…”

Section: Antig En -Uns Pecific and Additive A Pproache Smentioning

confidence: 99%

“…In contrast to epicutaneous immunotherapy, epicutaneous sensitization resulting in food allergy can occur when the skin barrier is damaged. TSLP‐elicited basophils promote epicutaneous sensitization to food antigens and subsequent IgE‐mediated food allergy through IL‐4, highlighting the need to develop better strategies that target the TSLP‐basophil‐IL‐4 axis in patients with atopic dermatitis to prevent the progression of allergies at distant mucosal sites . Treatment of mice with a monoclonal antibody specific to TSLP did prevent the development of food allergy, but combined treatment with antagonists to TSLP, IL‐25, and IL‐33 was required to suppress established food allergy …”

Section: Introductionmentioning

confidence: 99%

Recent developments and highlights in food allergy

Eiwegger

Hung

Diego

et al. 2019

Allergy

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The achievement of long-lasting, safe treatments for food allergy is dependent on the understanding of the immunological basis of food allergy. Accurate diagnosis is essential for management. In recent years, data from oral food challenges have revealed that routine allergy testing is poor at predicting clinical allergy for tree nuts, almonds in particular. More advanced antigen-based tests including component-resolved diagnostics and epitope reactivity may lead to more accurate diagnosis and selection of therapeutic intervention. Additional diagnostic accuracy may come from cellular tests such as the basophil activation test or mast cell approaches. In the context of clinical trials, cellular tests have revealed specific T-cell and B-cell populations that are more abundant in food-allergic individuals with distinct mechanistic features.Awareness of clinical markers, such as the ability to eat baked forms of milk and egg, continues to inform the understanding of natural tolerance development.Mouse models have allowed for investigation into multiple mechanisms of food allergy including modification of epithelial metabolism, and the induction of regulatory cell subsets and the microbiome. Increasing numbers of children who underwent food immunotherapy enlarged the body of evidence on mechanisms and predictors of treatment success. Experimental immunological markers in conjunction with clinical determinants such as lower age and lower initial specific IgE appear to be of benefit.More research on the optimal dose, preparation, and route of application integrating a high-level safety and efficacy is demanded. Alternatively, biologics blocking TSLP, IL-33, IL-4 and IL-13, or IgE may help to achieve that. K E Y W O R D Sallergy treatment, biologics, food allergy, immune tolerance, immunotherapy | 2357 EIWEGGER Et al.

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Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy

Cited by 132 publications

References 54 publications

Allergenicity reduction and rheology property of Lactobacillus‐fermented soymilk

Allergenicity reduction and rheology property of Lactobacillus‐fermented soymilk

Innate and adaptive type 2 immunity in lung allergic inflammation

Recent developments and highlights in food allergy

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