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    Development of a humanised mouse model of ovalbumin induced allergy and inflammation as a platform to test functional food


    Adams, Aine (2017) Development of a humanised mouse model of ovalbumin induced allergy and inflammation as a platform to test functional food. PhD thesis, National University of Ireland Maynooth.

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    Abstract

    Food allergies are most common during infancy Food allergy is a growing health problem with very limited treatment options For infants, cow’s milk protein allergy (CMPA) is the predominant food allergy, occurring in 2 - 7 5 % of population Infant formula which is often cow’s milk based, is the only approved alternative for breastfeeding However the proteins (casein and whey) in cow’s milk result in allergic symptoms in the infants These allergic symptoms can be avoided by providing the infants with hydrolysates of cow’s milk protein instead of the intact protein Whey protein hydrolysates, small bioactive peptide components of milk have been tested in mouse models for their anti-inflammatory/immunomodulatory properties however to date no studies have repeated efficacy of hydrolysates in a humanised mouse model setting In this study a large number of hydrolysates were screened in vitro to identify hydrolysates with anti-inflammatory properties In vitro we demonstrated that 147 hydrolysate significantly reduced DC maturation in a P-PARy dependent manner To mvestigate the anti-inflammatory potential of hydrolysate 147 in a human relevant model of food allergy we developed a novel humanised mouse model of OVA driven food allergy We directly compared two different strains of nonobese diabetic severe combined immunodeficient mice lacking the cytokine receptor common gamma chain (yc7') (NSG-SCF versus NSG- SGM3) expressing human cytokine genes for their suitability as a humanised mouse model Using NSG-SCF mice a human immune system was developed through engraftment of CD34+ hematopoietic stem cells Using an OVA sensitisation and challenge protocol the model of food allergy was developed in these humanised mice The capacity of hydro lysate 147 to mediate anti-inflammatory effects was examined through repeated administration of 147 hydrolysate after sensitisation and before challenge with OVA Both 147 hydrolysate and the wpc80 parent control equally reduced anaphylaxis. In comparison to wpc80 parent control, 147 reduced specific antibody responses, including OVA-specific IgGl, reduced the production of the pro- inflammatory cytokines IL-6, IL-17 and induced higher levels of the anti-inflammatory cytokine IL-10 in spleens and small intestines of OVA treated mice 147 in comparison to wpc80 was more potent at promoting a Thl/Th2 balance in the spleen and most significantly suppressed the accumulation of granulocyte populations in bone marrow and liver while simultaneously reducing the T , B and myeloid cell populations m the bone marrow of OVA mice For the first time, we have shown that a novel milk protein hydrolysate provided efficacy in comparison to its whey parent control in terms of reducing OVA driven allergy in a humanised mouse model This study demonstrated that 147 may prevent the development of other food allergies (egg-ova) in addition to CMPA (but not examined here) In addition this study, presents a framework, from which suitable conditions for testing functional foods, can be adopted in the development of novel agents for the prevention of allergic inflammation.

    Item Type: Thesis (PhD)
    Keywords: humanised mouse model; ovalbumin; induced allergy; inflammation; test; functional food;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Institute of Immunology
    Item ID: 13794
    Depositing User: IR eTheses
    Date Deposited: 11 Jan 2021 12:00
    URI:

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