ArticleThe Journal of allergy and clinical immunology2018
The vascular endothelial specific IL-4 receptor alpha-ABL1 kinase signaling axis regulates the severity of IgE-mediated anaphylactic reactions.
Article in The Journal of allergy and clinical immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling.Frontiers in immunology · 2022Trial
- S. aureus exposure during cutaneous antigen sensitization causes basophil- and interleukin-4-dependent exaggerated food anaphylaxis.Immunity · 2025Article
- Food allergy: begin at the skin, end at the mast cell?Nature reviews. Immunology · 2025Review
- Importance of mast cell histamine secretion in IgG-mediated systemic anaphylaxis.The Journal of allergy and clinical immunology · 2025Article
- IL-4-STAT6 axis amplifies histamine-induced vascular endothelial dysfunction and hypovolemic shock.The Journal of allergy and clinical immunology · 2024Article
- Acute systemic myeloid inflammatory and stress response in severe food allergic reactions.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2023Article
- IL-4 receptor alpha signaling alters oral food challenge and immunotherapy outcomes in mice.The Journal of allergy and clinical immunology · 2023Article
- IL-4 induces reparative phenotype of RPE cells and protects against retinal neurodegeneration via Nrf2 activation.Cell death & disease · 2022Article
- Pathophysiological, Cellular, and Molecular Events of the Vascular System in Anaphylaxis.Frontiers in immunology · 2022Review
- Biomarkers of PEGylated Liposomal Doxorubicin-Induced Hypersensitivity Reaction in Breast Cancer Patients Based on Metabolomics.Frontiers in pharmacology · 2022Article
- State-of-the-Art on Biomarkers for Anaphylaxis in Obstetrics.Life (Basel, Switzerland) · 2021Review
- Thermoneutrality Alters Gastrointestinal Antigen Passage Patterning and Predisposes to Oral Antigen Sensitization in Mice.Frontiers in immunology · 2021Article
- Genetic inhibition of NFATC2 attenuates asparaginase hypersensitivity in mice.Blood advances · 2020Article
- IL-4Rα expression by airway epithelium and smooth muscle accounts for nearly all airway hyperresponsiveness in murine allergic airway disease.Mucosal immunology · 2020Article
- Mechanisms of Dupilumab.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2020Review
- Recent advances in mechanisms of food allergy and anaphylaxis.F1000Research · 2020Review
- IL-13-induced intestinal secretory epithelial cell antigen passages are required for IgE-mediated food-induced anaphylaxis.The Journal of allergy and clinical immunology · 2019Article
- Abl family tyrosine kinases govern IgG extravasation in the skin in a murine pemphigus model.Nature communications · 2019Article
- Advances in drug allergy, urticaria, angioedema, and anaphylaxis in 2018.The Journal of allergy and clinical immunology · 2019Review
- Deletion of ΔdblGata motif leads to increased predisposition and severity of IgE-mediated food-induced anaphylaxis response.PloS one · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSevere IgE-mediated, food-induced anaphylactic reactions are characterized by pulmonary venous vasodilatation and fluid extravasation, which are thought to lead to the life-threatening anaphylactic phenotype. The underlying immunologic and cellular processes involved in driving fluid extravasation and the severe anaphylactic phenotype are not fully elucidated.
objectiveWe sought to define the interaction and requirement of IL-4 and vascular endothelial (VE) IL-4 receptor α chain (IL-4Rα) signaling in histamine-abelson murine leukemia viral oncogene homology 1 (ABL1)-mediated VE dysfunction and fluid extravasation in the severity of IgE-mediated anaphylactic reactions in mice.
methodsMice deficient in VE IL-4Rα and models of passive and active oral antigen- and IgE-induced anaphylaxis were used to define the requirements of the VE IL-4Rα and ABL1 pathway in severe anaphylactic reactions. The human VE cell line (EA.hy926 cells) and pharmacologic (imatinib) and genetic (short hairpin RNA knockdown of IL4RA and ABL1) approaches were used to define the requirement of this pathway in VE barrier dysfunction.
resultsIL-4 exacerbation of histamine-induced hypovolemic shock in mice was dependent on VE expression of IL-4Rα. IL-4- and histamine-induced ABL1 activation in human VE cells and VE barrier dysfunction was ABL1-dependent. Development of severe IgE-mediated hypovolemia and shock required VE-restricted ABL1 expression. Treatment of mice with a history of food-induced anaphylaxis with the ABL kinase inhibitor imatinib protected the mice from severe IgE-mediated anaphylaxis.
conclusionIL-4 amplifies IgE- and histamine-induced VE dysfunction, fluid extravasation, and the severity of anaphylaxis through a VE IL-4Rα/ABL1-dependent mechanism. These studies implicate an important contribution by the VE compartment in the severity of anaphylaxis and identify a new pathway for therapeutic intervention of IgE-mediated reactions.
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