title: Neuroimmune semaphorin 4A downregulates the severity of allergic response.
abstract: To define the role of semaphorin 4A (Sema4A) in allergic response, we employed Sema4A⁻/⁻ and wild-type (WT) mice in the experimental model of ovalbumin (OVA)-induced allergic airway inflammation. We observed a selective increase in eosinophilic airway infiltration accompanied by bronchial epithelial cell hyperplasia in allergen-treated Sema4A⁻/⁻ mice relative to WT mice. This enhanced inflammatory response was associated with a selective increase in bronchoalveolar lavage (BAL) interleukin 13 (IL-13) content, augmented airway hyperreactivity, and lower regulatory T cell (Treg) numbers. In vivo allergen-primed Sema4A⁻/⁻ CD4+ T cells were more effective in transferring T helper type 2 (Th2) response to naive mice as compared with WT CD4+ T cells. T-cell proliferation and IL-13 productions in OVA₃₂₃₋₃₃₉-restimulated Sema4A⁻/⁻ cell cultures were upregulated. Generated bone marrow chimeras showed an equal importance of both lung-resident cell and inflammatory cell Sema4A expression in optimal disease regulation. These data provide a new insight into Sema4A biology and define Sema4A as an important regulator of Th2-driven lung pathophysiology.
authors.affiliation: Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: E H
authors.initials: EH
authors.lastname: Nkyimbeng-Takwi
authors.forename: K
authors.initials: K
authors.lastname: Shanks
authors.forename: E
authors.initials: E
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Iyer
authors.forename: M M
authors.initials: MM
authors.lastname: Lipsky
authors.forename: L J
authors.initials: LJ
authors.lastname: Detolla
authors.forename: H
authors.initials: H
authors.lastname: Kikutani
authors.forename: A D
authors.initials: AD
authors.lastname: Keegan
authors.forename: S P
authors.initials: SP
authors.lastname: Chapoval
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000235:genetics* / Q000276:immunology*; D039961:Semaphorins / Q000235:genetics* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: C534721:Sema4A protein, mouse; D039961:Semaphorins; D010047:Ovalbumin