Browsing by Subject "allergy"
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- ItemOpen AccessInvestigating role of IL-4 receptor alpha (IL-4Ra) in murine models of atopic dermatitis(2021) Scibiorek, Martyna; Brombacher, F; Hadebe, SAtopic dermatitis (AD) is a common pruritic inflammatory skin disease with complex environmental and genetic predisposition factors. Primary skin barrier dysfunction and aberrant T helper 2 (TH2) responses to common allergens, together with increased serum IgE antibodies, characterise the disease. B and T cells are essential in the disease manifestation, however, the exact mechanism of how these cells are involved in skin sensitization to allergens is unclear. Clinical studies investigating the efficacy of monoclonal antibody to IgE such as omalizumab and ligelizumab do not show efficacy in AD patients. However, targeting IL-4/IL-13 signalling axis with dupilumab show efficacy in AD. We investigated the importance of interleukin 4 receptor alpha (IL- 4Rα) signalling specifically on B and T cells to understand the requirement of this signalling axis in epicutaneous skin sensitisation during AD. We investigated 3 models of AD using House dust mite (HDM), Ovalbumin (OVA) and low-calcemic analog of vitamin D (MC903) on mouse strains lacking IL-4Ra on various B and T cells. We used mb1creIL-4Rα-/lox (mice lacking IL-4Rα on B cells), iLcKCre IL-4Rα-/lox (mice lacking IL-4Rα on all T cells), LcKCre IL-4Rα-/lox (mice lacking IL-4Rα on CD4+ and CD8+ T cells), CD4Cre IL-4Rα-/lox (mice lacking IL-4Rα on CD4+ Tcells), Foxp3Cre IL-4Rα-/lox (mice lacking IL-4Rα on Foxp3+ T regulatory cells) and IL-4Rα-/lox littermate controls. We analysed cellular infiltrate in the skin and inguinal lymph nodes (LN) by flow cytometry, histology of the skin, serum antibodies and cytokines by ELISA. Mice lacking IL-4Rα-responsive B cells showed a reduced serum IgE levels, but no significant differences in epidermal thickening compared to littermate control in HDM or MC903 models. Mice investigated in the T cell arm of the study showed reduced epidermal thickening in pan-T cell IL-4Rα knock-out, but not in groups lacking IL-4Rα signalling in adaptive T cells, suggesting importance of IL4/IL13 signalling axis in ydT cells during AD. Overall, our results suggest that deletion of IL-4Rα on innate T cells regulates inflammatory response in atopic dermatitis.
- ItemOpen AccessJet lag and environmental conditions that may influence exercise performance during the 2010 FIFA World Cup in South Africa(2010) Schwellnus, Martin; Derman, EltonThe 2010 FIFA World Cup will be held in South Africa in June/July 2010. This is the largest international sports event ever to be held in this country. At this time 32 international football teams, with their management and supporters, will travel to South Africa. These players and visitors will be exposed to changes in time zones (those travelling from continents in the East and West) as well as different environmental conditions. In particular, for the players, the achievement of peak sporting performance during this event is most important. It is well established that, in order to achieve peak exercise performance, many variables need to be optimised. These variables include physical and mental training, rest, nutrition, team dynamics and tactics. However, adjustments to differences in time zones as well as environmental factors on and around the playing field can also have a significant impact on exercise performance. In this review, the potential effects of “jet lag”, as well as several important environmental conditions, on exercise performance will be discussed. The climatic, atmospheric and weather conditions that are likely to be prevalent in each of the South African host cities at the time of the 2010 FIFA World Cup will be reviewed. Finally, practical recommendations to deal with the effects of jet lag, as well as guidelines to optimise performance under different environmental conditions that are expected during the 2010 FIFA World Cup, will be provided.