Investigating role of IL-4 receptor alpha (IL-4Ra) in murine models of atopic dermatitis

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dc.contributor.advisorBrombacher, F
dc.contributor.advisorHadebe, S
dc.contributor.authorScibiorek, Martyna
dc.date.accessioned2023-02-23T10:14:13Z
dc.date.available2023-02-23T10:14:13Z
dc.date.issued2021
dc.date.updated2022-11-23T10:17:06Z
dc.description.abstractAtopic 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.
dc.identifier.apacitationScibiorek, M. (2021). <i>Investigating role of IL-4 receptor alpha (IL-4Ra) in murine models of atopic dermatitis</i>. (). ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. Retrieved from http://hdl.handle.net/11427/37016en_ZA
dc.identifier.chicagocitationScibiorek, Martyna. <i>"Investigating role of IL-4 receptor alpha (IL-4Ra) in murine models of atopic dermatitis."</i> ., ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2021. http://hdl.handle.net/11427/37016en_ZA
dc.identifier.citationScibiorek, M. 2021. Investigating role of IL-4 receptor alpha (IL-4Ra) in murine models of atopic dermatitis. . ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. http://hdl.handle.net/11427/37016en_ZA
dc.identifier.ris TY - Doctoral Thesis AU - Scibiorek, Martyna AB - Atopic 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. DA - 2021_ DB - OpenUCT DP - University of Cape Town KW - atopic dermatitis KW - interleukin 4 receptor alpha KW - allergy KW - T cells KW - B cells KW - murine model LK - https://open.uct.ac.za PY - 2021 T1 - Investigating role of IL-4 receptor alpha (IL-4Ra) in murine models of atopic dermatitis TI - Investigating role of IL-4 receptor alpha (IL-4Ra) in murine models of atopic dermatitis UR - http://hdl.handle.net/11427/37016 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/37016
dc.identifier.vancouvercitationScibiorek M. Investigating role of IL-4 receptor alpha (IL-4Ra) in murine models of atopic dermatitis. []. ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2021 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/37016en_ZA
dc.language.rfc3066eng
dc.publisher.departmentDepartment of Clinical Laboratory Sciences
dc.publisher.facultyFaculty of Health Sciences
dc.subjectatopic dermatitis
dc.subjectinterleukin 4 receptor alpha
dc.subjectallergy
dc.subjectT cells
dc.subjectB cells
dc.subjectmurine model
dc.titleInvestigating role of IL-4 receptor alpha (IL-4Ra) in murine models of atopic dermatitis
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationlevelPhD
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