Dokument: Progranulin Prevents Regulatory NK Cell Cytotoxicity Against Antiviral T Cells
| Titel: | Progranulin Prevents Regulatory NK Cell Cytotoxicity Against Antiviral T Cells | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=56260 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20210521-082813-2 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Huang, Anfei [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Philipp Lang [Gutachter] Prof. Jörg Timm [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | NK cell-mediated regulation of antigen-specific T cells can contribute to and exacerbate chronic viral infection, but the protective mechanisms against NK cell-mediated attack on T cell immunity are poorly understood.
Here, we show that progranulin (PGRN) can reduce NK cell cytotoxicity through reduction of NK cell expansion, granzyme B transcription, and NK cell-mediated lysis of target cells. Following infection with the lymphocytic choriomeningitis virus (LCMV), PGRN levels increased, a phenomenon dependent on the presence of macrophages and type I IFN signaling. Absence of PGRN in mice (Grn–/–) resulted in enhanced NK cell activity, increased NK cell-mediated killing of antiviral T cells, reduced antiviral T cell immunity, and increased viral burden, culminating in increased liver immunopathology. However, both naïve or LCMV infected Grn–/– mice showed the comparable NK development and NK cell expression of surface activating or inhibitory receptors to WT mice. In addition, PGRN may not have any effects on virus replication and also on T cell development and activation, suggesting the extrinsic role of PGRN to T cell. Depletion of NK cells restored antiviral immunity and alleviated pathology during infection in Grn–/– mice. In turn, PGRN treatment improved antiviral T cell immunity. Taken together, we identified PGRN as a critical factor capable of reducing NK cell–mediated attack of antiviral T cells. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät » Institute » Institut für Molekulare Medizin | |||||||
| Dokument erstellt am: | 21.05.2021 | |||||||
| Dateien geändert am: | 21.05.2021 | |||||||
| Promotionsantrag am: | 19.01.2021 | |||||||
| Datum der Promotion: | 12.05.2021 |
