title: Semaphorin 3E Deficiency Exacerbates Airway Inflammation, Hyperresponsiveness, and Remodeling in a Mouse Model of Allergic Asthma.
abstract: Semaphorin 3E (Sema3E) plays a crucial role in axon guidance, vascular patterning, and immune regulation. Nevertheless, the role of Sema3E in asthma is still elusive. In this study, we show that genetic ablation of Sema3E in mice results in increased lung granulocytosis, airway hyperresponsiveness, mucus overproduction, collagen deposition, and Th2/Th17 inflammation. Transfer ofSema3e-/-bone marrow progenitor cells to irradiated wild-type (WT) recipients exacerbates airway hyperresponsiveness and inflammation, whereas transfer of WT bone marrow progenitor cells ameliorates asthma pathology inSema3e-/-recipients.Sema3e-/-mice display a higher frequency of CD11b+pulmonary dendritic cells than their WT controls at the baseline and after sensitization with house dust mite. Adoptive transfer of CD11b+pulmonary dendritic cells fromSema3e-/-mice into WT recipients increases house dust mite-induced Th2/Th17 inflammation in the airway. Together, these findings identify Sema3E as a novel regulatory molecule in allergic asthma that acts upstream of proallergic events and suggest that targeting this molecule could be a novel approach to treat allergic asthma.
authors.affiliation: Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada; and.
authors.forename: Hesam
authors.identifier: 0000-0002-0205-1069
authors.initials: H
authors.lastname: Movassagh
authors.affiliation: Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada; and.
authors.forename: Lianyu
authors.initials: L
authors.lastname: Shan
authors.affiliation: Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada; and.
authors.forename: Ashfaque
authors.initials: A
authors.lastname: Mohammed
authors.affiliation: Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada; and.|Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba R3E 0T5 Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Halayko
authors.affiliation: Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada; and abdel.gounni@umanitoba.ca.
authors.forename: Abdelilah S
authors.identifier: 0000-0003-1265-6560
authors.initials: AS
authors.lastname: Gounni
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003598:Cytoskeletal Proteins; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D007249:Inflammation / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000503:physiopathology; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D039981:Pyroglyphidae / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D039961:Semaphorins; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; C111150:Sema3e protein, mouse; D039961:Semaphorins