PlexinD1 deficiency in macrophage exacerbates house dust mite-induced allergic asthma

dc.contributor.authorAktar, Amena
dc.contributor.examiningcommitteeFowke, Keith (Medical Microbiology and Infectious Diseases) Mookherjee, Neeloffer (Internal Medicine) Murooka, Thomas (Immunology)en_US
dc.contributor.supervisorSoussi Gounni, Abdelilah (Immunology)en_US
dc.date.accessioned2020-01-07T14:13:23Z
dc.date.available2020-01-07T14:13:23Z
dc.date.issued2019-12-18en_US
dc.date.submitted2019-12-18T18:21:36Zen
dc.date.submitted2020-01-06T20:24:58Zen
dc.degree.disciplineImmunologyen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractSemaphorin3E (Sema3E) and its receptor plexinD1 are involved in cell migration, proliferation, and angiogenesis considered key features of asthma. The absence of Sema3E exacerbates asthma features, and treatment with recombinant Sema3E reduces inflammation and airway hyperresponsiveness (AHR). However, whether Sema3E-plexinD1 axis regulates airway macrophages function in allergic asthma has not been studied. Therefore, we investigated the role of plexinD1 deficient macrophage in allergic asthma. Genetic ablation of plexinD1 receptor in interstitial macrophages was performed in vivo by crossing CX3CR1Cre/ERT with Plxnd1 floxed mice followed by tamoxifen treatment. AHR, airway inflammation and remodeling were measured by flexivent, flow cytometry, histochemistry, ELISA, and RT-PCR techniques respectively. We found that the absence of Plxnd1 in lung interstitial macrophages increased AHR, airway leukocytes number, allergen-specific IgE, goblet cell hyperplasia, and Th2/Th17 cytokines response in the acute house dust mite model of allergic asthma. Also, the expression of Muc5ac, Muc5b and α-SMA genes were increased in mice with Plxnd1 deficient interstitial macrophage compared to WT mice. Our data suggest that lung interstitial macrophage via Sema3E/plexinD1 axis negatively regulates airway inflammation, AHR, and airway remodeling in a murine model of allergic asthma.en_US
dc.description.noteFebruary 2020en_US
dc.identifier.urihttp://hdl.handle.net/1993/34451
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectAsthmaen_US
dc.titlePlexinD1 deficiency in macrophage exacerbates house dust mite-induced allergic asthmaen_US
dc.typemaster thesisen_US
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