Characterisation of an “eat-me” signal on dying and HIV-1-infected T cells

<p>The clearance of dying cells by phagocytes, termed efferocytosis, is regulated by a combination of “eat-me” and “don’t eat-me” signals expressed on the dying cell surface. Efferocytosis is essential for ontogeny and tissue homeostasis, but can also mediate the spread of pathogen infection,...

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Bibliographic Details
Main Author: Karaji, N
Other Authors: Sattentau, Q
Format: Thesis
Published: 2018
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author Karaji, N
author2 Sattentau, Q
author_facet Sattentau, Q
Karaji, N
author_sort Karaji, N
collection OXFORD
description <p>The clearance of dying cells by phagocytes, termed efferocytosis, is regulated by a combination of “eat-me” and “don’t eat-me” signals expressed on the dying cell surface. Efferocytosis is essential for ontogeny and tissue homeostasis, but can also mediate the spread of pathogen infection, and its dysregulation leads to inflammatory disorders. The Sattentau laboratory recently reported that the macrophage efferocytic uptake of HIV-1-infected CD4+ T cells drives efficient infection of macrophages. However, the signals involved in the macrophage capture of the infected T cell remain undefined, but cell death appears to be an important component of this recognition. </p> <p>In this study a novel efferocytic pathway which is based on the cleavage of the heavily sialylated glycoprotein CD43 acting as a potent ‘don’t eat-me’ signal for macrophages is investigated. Data presented in this thesis imply that; i) CD43 shedding is mediated by ADAM10 which is activated by T cell death, and ii) cleavage of CD43 as a don’t eat-me signal from the surface of dying and infected T cells triggers their engulfment by macrophages. </p> <p>In the context of HIV-1infection, interventions in this pathway may have the potential of reducing targeted macrophage infection. Also, the knowledge of this novel efferocytic pathway has general implications for understanding and potentially treating unwanted inflammatory disorders.</p>
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spelling oxford-uuid:666f4931-d692-47b7-af7b-d68a7e25bbbf2024-12-11T11:30:23ZCharacterisation of an “eat-me” signal on dying and HIV-1-infected T cellsThesishttp://purl.org/coar/resource_type/c_db06uuid:666f4931-d692-47b7-af7b-d68a7e25bbbfORA Deposit2018Karaji, NSattentau, QRussell, R<p>The clearance of dying cells by phagocytes, termed efferocytosis, is regulated by a combination of “eat-me” and “don’t eat-me” signals expressed on the dying cell surface. Efferocytosis is essential for ontogeny and tissue homeostasis, but can also mediate the spread of pathogen infection, and its dysregulation leads to inflammatory disorders. The Sattentau laboratory recently reported that the macrophage efferocytic uptake of HIV-1-infected CD4+ T cells drives efficient infection of macrophages. However, the signals involved in the macrophage capture of the infected T cell remain undefined, but cell death appears to be an important component of this recognition. </p> <p>In this study a novel efferocytic pathway which is based on the cleavage of the heavily sialylated glycoprotein CD43 acting as a potent ‘don’t eat-me’ signal for macrophages is investigated. Data presented in this thesis imply that; i) CD43 shedding is mediated by ADAM10 which is activated by T cell death, and ii) cleavage of CD43 as a don’t eat-me signal from the surface of dying and infected T cells triggers their engulfment by macrophages. </p> <p>In the context of HIV-1infection, interventions in this pathway may have the potential of reducing targeted macrophage infection. Also, the knowledge of this novel efferocytic pathway has general implications for understanding and potentially treating unwanted inflammatory disorders.</p>
spellingShingle Karaji, N
Characterisation of an “eat-me” signal on dying and HIV-1-infected T cells
title Characterisation of an “eat-me” signal on dying and HIV-1-infected T cells
title_full Characterisation of an “eat-me” signal on dying and HIV-1-infected T cells
title_fullStr Characterisation of an “eat-me” signal on dying and HIV-1-infected T cells
title_full_unstemmed Characterisation of an “eat-me” signal on dying and HIV-1-infected T cells
title_short Characterisation of an “eat-me” signal on dying and HIV-1-infected T cells
title_sort characterisation of an eat me signal on dying and hiv 1 infected t cells
work_keys_str_mv AT karajin characterisationofaneatmesignalondyingandhiv1infectedtcells