Semaphorin3E is a novel regulator of IgE through regulation of germinal center responses in a mouse model of allergic asthma

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dc.contributor.authorSedaghat, Fatemeh
dc.contributor.examiningcommitteeMarshall, Aaron (Immunology)
dc.contributor.examiningcommitteeMurooka, Thomas (Immunology)
dc.contributor.supervisorSoussi Gounni, Abdelilah
dc.date.accessioned2024-12-13T17:20:54Z
dc.date.available2024-12-13T17:20:54Z
dc.date.issued2024-12-10
dc.date.submitted2024-12-10T19:44:40Zen_US
dc.degree.disciplineImmunology
dc.degree.levelMaster of Science (M.Sc.)
dc.description.abstractSemaphorin3E (Sema3E) is a protein that plays a critical role in immunity to diseases, including asthma, by regulating cell migration, proliferation, and angiogenesis. Little is known about the role of Sema3E in immunoglobulin E (IgE) regulation. Recent data showed that Sema3e-/- mice have a significantly higher serum level of total and allergen-specific IgE in allergic asthma. These results strongly indicate a crucial involvement of Sema3E in modulating IgE production. In my project, we hypothesised that Sema3E negatively regulates IgE levels through germinal center (GC) responses. To investigate the regulatory role of Sema3E in IgE production and GC formation, Sema3e-/- and WT mice underwent an acute HDM challenge. Flow cytometry was performed to investigate the number of GC B cells, T follicular helper (Tfh) cells, and inflammatory cells. The antibodies and inflammatory cytokines levels were detected by ELISA and Mesoscale, respectively. Immunofluorescence (IF) staining and H&E staining were performed to investigate GC formation and lung inflammation, respectively. Additionally, to check if Sema3E plays a role through the ICOS/ICOS-L pathway, GC formation was blocked by intraperitoneal administration of anti-ICOS-L or rat IgG as an isotype control. The results demonstrated that at the steady-state, Sema3e-/- mice had a significantly higher baseline number of GC B cells, Tfh cells, plasmablasts, plasma cells, and serum IgE and IgG1 than the WT counterparts. Interestingly, baseline expression of IgE and IgG by B cells is regulated by Sema3E, and Sema3e-/- mice demonstrated higher expression of IgE and IgG1 in their B cells. Upon immunization with HDM, Sema3e-/- mice exhibited enhanced GC responses, IgE production, and lung inflammation. We demonstrated that the deletion of Sema3E in mice led to an increase in the expression of ICOS on CD4+ T cells and disruption of ICOS/ICOS-L signalling, remarkably reducing the number of inflammatory cells, plasma cells, serum levels of IgE and IgG1, and lung inflammation indicating the importance of ICOS/ICOS-L signalling pathway in Sema3E regulatory effect. In conclusion, Sema3E plays a critical regulatory role in GC response and IgE production at the steady-state and post-immunization through ICOS/ICOS-L signalling, suggesting the critical negative regulatory role of Sema 3E in allergic inflammation.
dc.description.noteFebruary 2025
dc.identifier.urihttp://hdl.handle.net/1993/38707
dc.language.isoeng
dc.rightsopen accessen_US
dc.subjectSemaphorin3E
dc.subjectIgE
dc.subjectGerminal center
dc.subjectAllergic asthma
dc.subjectB cells
dc.subjectT follicular helper cells (Tfh)
dc.titleSemaphorin3E is a novel regulator of IgE through regulation of germinal center responses in a mouse model of allergic asthma
dc.typemaster thesisen_US
local.subject.manitobano
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