Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596324
Title: Investigating the roles of IL-25 in type-2 immunity
Author: Ballantyne, Sarah Jane
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2008
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Abstract:
I125-/- animals, generated in the laboratory, were used to assess the role of IL-25 during initiation of immune responses. Expulsion of Nippostrongylus brasiliensis, an intestinal parasite, has been shown to be critically dependent on rapid production of the type-2 cytokines IL-4 and IL-13. IL-25 deficient animals failed to expel N. brasiliensis efficiently and this correlated with a delay in type-2 cytokine production. Conversely, administration of exogenous IL-25 induced a rapid parasite expulsion that was independent of T or B cells but required type-2 cytokine expression. Analysis of the draining (mesenteric) lymph nodes by flow cytometry revealed a novel non-B/non-T, c-kit+, FcεR1- cell population induced following infection of wildtype animals but absent in the lymph nodes of infected il25-/- mice. This population, which was also induced following administration of recombinant IL-25 protein, expressed IL-4 and IL-13 mRNA. These data clearly demonstrate the critical role IL-25 plays during initiation of protective Th2 responses. To investigate whether IL-25 also plays a role in atopic disease, a neutralising anti-IL-25 antibody was generated and then assessed in a murine model of allergic airway disease. This protocol replicates the major features found in human asthma including airway hyperresponsiveness (AHR). Administration of anti-IL-25 blocking antibody prior to sensitisation and pulmonary challenge completely abrogated airway inflammation and AHR. Significantly, when pre-sensitised animals were treated with anti-IL-25 antibody only during antigen challenge in the lung, AHR was still blocked. IL-25 regulates airway inflammation and AHR partially by modulating local levels of IL-13 and IL-17; indeed the inhibitory effects of anti-IL-25 antibody were reversed by co-administration of a neutralising anti-IL-17 antibody. However, analysis of mice deficient in IL-4, IL-5, IL-9 and IL-13 suggest that IL-25 can also modulate AHR via a type-2 cytokine independent mechanism.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.596324  DOI: Not available
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