Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.592742
Title: The role of interleukin-31 in human allergic disease
Author: Stott, Bryony Alexandra
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Abstract:
The newly described cytokine Interleukin (IL) 31 has been shown to be expressed by murine activated T lymphocytes of a Th2 phenotype. Like IL-17 and IL-22, IL-31 is a tissue signalling cytokine whose receptor is mainly found on non-immune cells. An over-abundance of IL-31has been demonstrated in atopic diseases of the skin and transgenic mice engineered to over-express IL-31develop the symptoms of atopic dermatitis (AD) such as pruritus, inflammation and alopecia. Allergic asthma and rhinitis share characteristics of AD such as pruritus and Th2 cell driven inflammation but the role IL-31 may play in these diseases is unknown. The aim of this thesis was threefold; firstly to investigate whether IL-31 is expressed in the airway and peripheral blood mononuclear cells (PBMC) derived from patients with allergic rhinitis. Secondly, this study explored the regulation of IL-31 expression from T-cells to understand the conditions under which IL-31 is expressed and investigate whether IL-31 is a Th2 cytokine like IL-4 and IL-13. Finally we investigated the function of IL-31, with respect to its effect on normal human bronchial epithelial cells (NHBE). The influence of IL-31 on the gene expression of NHBE was comprehensively investigated with a single colour whole genome microarray. Basal IL-31 expression was higher in PBMC from atopic donors compared to healthy controls and very strongly up-regulated in response to allergen stimulation. IL-31 protein was also detected in skin and nasal biopsies by immunohistochemistry. IL-31 was expressed by Th2 T-cell clones and not by Th1, Th17 or Th22. This expression was dependent on autocrine IL-4 expression and even Th1 clones were able to express IL-31 if IL-4 was added to culture. IL-31 alone had a marginal effect on the gene expression of NHBE but was found to act in synergy with Th2 cytokines to amplify the expression of pro-inflammatory chemokines and growth factors. Taken together, IL-31 appears to be a cytokine induced by allergen stimulation that can enhance and maintain allergic inflammation.
Supervisor: Schmidt-Weber, Carsten ; Durham, Stephen Sponsor: National Heart and Lung Institute
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.592742  DOI: Not available
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