IgE and anaphylaxis specific to the carbohydrate alpha-gal depend on IL-4

Hils, Miriam; Hoffard, Nils; Iuliano, Caterina; Kreft, Luisa; Chakrapani, Neera; Swiontek, Kyra; Fischer, Konrad; Eberlein, Bernadette; Köberle, Martin; Fischer, Jörg; Hilger, Christiane; Ohnmacht, Caspar; Kaesler, Susanne; Wölbing, Florian; Biedermann, Tilo

doi:10.1016/j.jaci.2023.12.003

Cited by 2 publications

(1 citation statement)

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“…To understand and ultimately to prevent the development of red meat allergy, predictive animal models are necessary that best reflect the pathophysiology in humans. Mice have been an essential model to examine the function of the host’s immune system after tick bites ( 25 ) and to assess the role of immune cells and cytokines, such as IL-4, during allergy development ( 26 ). However, mice differ to humans in aspects important to allergy research, such as the structure of the skin and the diet ( 27 ).…”

Section: Introductionmentioning

confidence: 99%

Gene-edited pigs: a translational model for human food allergy against alpha-Gal and anaphylaxis

Wang,

Hils,

Fischer

et al. 2024

Front. Immunol.

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The prevalence of food allergy is rising and is estimated to approach 10%. Red meat allergy is the first known food allergy elicited by immunoglobulin E (IgE) antibodies recognizing a carbohydrate. Due to the loss of function of the alpha−1,3−galactosyltransferase (GGTA1) gene in humans, the disaccharide galactose-α-1,3-galactose (α-Gal) cannot be synthesized and therefore became immunogenic. IgE sensitization is elicited through the skin by repetitive tick bites transmitting α-Gal. The underlying mechanisms regarding innate and adaptive immune cell activation, including the B-cell isotype switch to IgE, are poorly understood, requiring further research and physiologically relevant animal models. Here, we describe a new animal model of red meat allergy using percutaneous α-Gal sensitization of gene-edited GGTA1-deficient pigs. Total and α-Gal-specific IgG, IgG1, IgG2, IgG4, and IgE levels were tracked. Further key factors associated with allergic skin inflammation, type 2 immunity, and allergy development were measured in PBMCs and skin samples. Significant increases in α-Gal-specific IgG1 and IgE levels indicated successful sensitization to the allergen α-Gal. Intracutaneous sensitizations with α-Gal recruited lymphocytes to the skin, including elevated numbers of T helper 2 (Th2) cells. Finally, α-Gal-sensitized pigs not only recognized α-Gal as non-self-antigen following α-Gal exposure through the skin but also developed anaphylaxis upon antigen challenge. Based on the similarities between the porcine and human skin, this new large animal model for α-Gal allergy should help to unveil the consecutive steps of cutaneous sensitization and aid the development of prophylactic and treatment interventions.

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Section: Introductionmentioning

confidence: 99%

Gene-edited pigs: a translational model for human food allergy against alpha-Gal and anaphylaxis

Wang,

Hils,

Fischer

et al. 2024

Front. Immunol.

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PGRN Inhibits Early B‐cell Activation and IgE Production Through the IFITM3‐STAT1 Signaling Pathway in Asthma

Zhang,

Ruan,

Yang

et al. 2024

Advanced Science

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Progranulin (PGRN) plays a critical role in bronchial asthma and the function of various immune cells. However, the mechanisms by which PGRN influences B‐cell receptor (BCR) signaling and immunoglobulin E(IgE) production are not fully understood. The study aimed to elucidate the molecular mechanisms through which PGRN affects BCR signaling, B‐cell differentiation, and IgE production. A PGRN knockout mouse model, along with techniques including flow cytometry, the creation of a bone marrow chimeric mouse model, total internal reflection fluorescence (TIRF), and Western blot (WB) analysis is employed, to investigate the link between PGRN and various aspects of B‐cell biology. It is discovered that the absence of PGRN in mice alters peripheral B‐cell subpopulations, promotes IgE class switching in a cell‐intrinsic manner, and affects B‐cell subpopulations. Additionally, PGRN modulates B‐cell functions by regulating BCR signaling pathways, metabolic processes, and the actin cytoskeleton during early B‐cell activation. Significantly, PGRN deficiency results in diminished production of NP‐specific antibodies. Moreover, it is found that PGRN inhibits B‐cell activation and IgE production through the PGRN‐IFITM3‐STAT1 signaling pathway. The findings provide new strategies for the targeted treatment of bronchial asthma, highlighting the crucial role of PGRN in B‐cell signaling and IgE production.

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IgE and anaphylaxis specific to the carbohydrate alpha-gal depend on IL-4

Cited by 2 publications

References 61 publications

Gene-edited pigs: a translational model for human food allergy against alpha-Gal and anaphylaxis

Gene-edited pigs: a translational model for human food allergy against alpha-Gal and anaphylaxis

PGRN Inhibits Early B‐cell Activation and IgE Production Through the IFITM3‐STAT1 Signaling Pathway in Asthma

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