title: IgE-activated basophils regulate eosinophil tissue entry by modulating endothelial function.
abstract: Vertebrate immunity has evolved a modular architecture in response to perturbations. Allergic inflammation represents such a module, with signature features of antigen-specific IgE and tissue eosinophilia, although the cellular and molecular circuitry coupling these responses remains unclear. Here, we use genetic and imaging approaches in models of IgE-dependent eosinophilic dermatitis to demonstrate a requisite role for basophils. After antigenic inflammation, basophils initiate transmigration like other granulocytes but, upon activation via their high-affinity IgE receptor, alter their migratory kinetics to persist at the endothelium. Prolonged basophil-endothelial interactions, in part dependent on activation of focal adhesion kinases, promote delivery of basophil-derived IL-4 to the endothelium and subsequent induction of endothelial vascular cell adhesion molecule-1 (VCAM-1), which is required for eosinophil accumulation. Thus, basophils are gatekeepers that link adaptive immunity with innate effector programs by altering access to tissue sites by activation-induced interactions with the endothelium.
authors.affiliation: Department of Pediatrics, Department of Medicine, Department of Anatomy, Sandler Asthma Basic Research Center, Cardiovascular Research Institute, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143 Department of Pediatrics, Department of Medicine, Department of Anatomy, Sandler Asthma Basic Research Center, Cardiovascular Research Institute, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Laurence E
authors.initials: LE
authors.lastname: Cheng
authors.affiliation: Department of Pediatrics, Department of Medicine, Department of Anatomy, Sandler Asthma Basic Research Center, Cardiovascular Research Institute, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Sullivan
authors.affiliation: Department of Pediatrics, Department of Medicine, Department of Anatomy, Sandler Asthma Basic Research Center, Cardiovascular Research Institute, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Lizett E
authors.initials: LE
authors.lastname: Retana
authors.affiliation: Department of Pediatrics, Department of Medicine, Department of Anatomy, Sandler Asthma Basic Research Center, Cardiovascular Research Institute, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143 Department of Pediatrics, Department of Medicine, Department of Anatomy, Sandler Asthma Basic Research Center, Cardiovascular Research Institute, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143 Department of Pediatrics, Department of Medicine, Department of Anatomy, Sandler Asthma Basic Research Center, Cardiovascular Research Institute, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Christopher D C
authors.initials: CD
authors.lastname: Allen
authors.affiliation: Department of Pediatrics, Department of Medicine, Department of Anatomy, Sandler Asthma Basic Research Center, Cardiovascular Research Institute, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143.
authors.forename: Hong-Erh
authors.initials: HE
authors.lastname: Liang
authors.affiliation: Department of Pediatrics, Department of Medicine, Department of Anatomy, Sandler Asthma Basic Research Center, Cardiovascular Research Institute, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143 Department of Pediatrics, Department of Medicine, Department of Anatomy, Sandler Asthma Basic Research Center, Cardiovascular Research Institute, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143 Department of Pediatrics, Department of Medicine, Department of Anatomy, Sandler Asthma Basic Research Center, Cardiovascular Research Institute, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143 Department of Pediatrics, Department of Medicine, Department of Anatomy, Sandler Asthma Basic Research Center, Cardiovascular Research Institute, Department of Microbiology and Immunology, and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143 locksley@medicine.ucsf.edu.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Locksley
mesh_terms: D000818:Animals; D001491:Basophils / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication; D003872:Dermatitis / Q000276:immunology / Q000473:pathology; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D007113:Immunity, Innate / Q000235:genetics; D007073:Immunoglobulin E / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D057705:Transendothelial and Transepithelial Migration / Q000235:genetics / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology
chemical_list: D019010:Vascular Cell Adhesion Molecule-1; D015847:Interleukin-4; D007073:Immunoglobulin E