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• W625392023 abstract "The aim of this work was to investigate immune modulation with a particular focus onairway inflammation and allergic pathogenesis. This was probed in a model of pathogendriven immunomodulation (B. pertussis), and two models of therapeutic intervention namelyimmunisation (attenuated B. pertussis, BPZE1) or using a candidate cell therapy approach(mesenchymal stem cells, MSC).This work demonstrated that, in contrast to virulent B. pertussis, an attenuated,candidate vaccine strain of B. pertussis, BPZE1, did not enhance but rather reduced allergendrivenairway pathology supporting findings that suggest allergic asthma is linked not just toa CD4+ T cell profile, but also to the degree of airway damage at the time of priming. Thesecond approach sought to ascertain whether a candidate stem cell therapy could modulateimmunity in vivo to a degree that was sufficient to suppress allergic lung inflammation. Thework presented here demonstrated that adult bone marrow-derived allogeneic MSC activelyprevent the induction of allergen driven pathology in a murine model. Prior stimulation ofMSC with IFN-γ increased their protective effect. An increase in IL-10 as a result of MSCdelivery suggested a role for MSC in Treg induction. The immune mechanisms by whichMSC confer protection in this model were probed and demonstrated that MSC generate theexpansion of Treg subsets, CD4+FoxP3 and CD8+ γ/δ T cells, in the lung. Moreover,expansion of Treg was proven to exert a functional effect as depletion of these cells resulted ina negation of the protective effect of MSC. In an experimental asthma model, where micedevoid of naturally occurring Treg, delivery of MSC fails to impair the development ofallergic airway pathology and class switching to IgE.A reduction in airway eosinophilia in the absence of regulatory T cells suggested analternative mechanism of protection employed by MSC. Pre-incubation with MSC inhibitedthe expression of important adhesion markers on eosinophils which most likely affected their ability to migrate as demonstrated by the inhibitory effect on their chemotactic migration.These data suggests a critical role for soluble factor secretion by MSC contributing to thereduction of airway eosinophilia. Collectively, these data provides a fundamental insight intonovel therapeutic approaches that can profoundly influence the allergic airway response." @default.
• W625392023 created "2016-06-24" @default.
• W625392023 creator A5014811638 @default.
• W625392023 date "2010-02-01" @default.
• W625392023 modified "2023-09-24" @default.
• W625392023 title "Stem Cell and Biological Interventions to treat Allergic Airway Disease" @default.
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