A role for phagocytosis in inducing cell death during thymocyte negative selection
Autoreactive thymocytes are eliminated during negative selection in the thymus, a process important for establishing self-tolerance. Thymic phagocytes serve to remove dead thymocytes, but whether they play additional roles during negative selection remains unclear. Here, using a murine thymic slice...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/48097 |
| _version_ | 1811181522487607296 |
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| author | Nadia S Kurd Lydia K Lutes Jaewon Yoon Shiao Wei Chan Ivan L Dzhagalov Ashley R Hoover Ellen A Robey |
| author_facet | Nadia S Kurd Lydia K Lutes Jaewon Yoon Shiao Wei Chan Ivan L Dzhagalov Ashley R Hoover Ellen A Robey |
| author_sort | Nadia S Kurd |
| collection | DOAJ |
| description | Autoreactive thymocytes are eliminated during negative selection in the thymus, a process important for establishing self-tolerance. Thymic phagocytes serve to remove dead thymocytes, but whether they play additional roles during negative selection remains unclear. Here, using a murine thymic slice model in which thymocytes undergo negative selection in situ, we demonstrate that phagocytosis promotes negative selection, and provide evidence for the escape of autoreactive CD8 T cells to the periphery when phagocytosis in the thymus is impaired. We also show that negative selection is more efficient when the phagocyte also presents the negative selecting peptide. Our findings support a model for negative selection in which the death process initiated following strong TCR signaling is facilitated by phagocytosis. Thus, the phagocytic capability of cells that present self-peptides is a key determinant of thymocyte fate. |
| first_indexed | 2024-04-11T09:18:49Z |
| format | Article |
| id | doaj.art-fffba24565fc4ed5a994274e6a024134 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:18:49Z |
| publishDate | 2019-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-fffba24565fc4ed5a994274e6a0241342022-12-22T04:32:15ZengeLife Sciences Publications LtdeLife2050-084X2019-12-01810.7554/eLife.48097A role for phagocytosis in inducing cell death during thymocyte negative selectionNadia S Kurd0Lydia K Lutes1Jaewon Yoon2Shiao Wei Chan3Ivan L Dzhagalov4Ashley R Hoover5Ellen A Robey6https://orcid.org/0000-0002-3630-5266Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDivision of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDivision of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDivision of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDivision of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDivision of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDivision of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesAutoreactive thymocytes are eliminated during negative selection in the thymus, a process important for establishing self-tolerance. Thymic phagocytes serve to remove dead thymocytes, but whether they play additional roles during negative selection remains unclear. Here, using a murine thymic slice model in which thymocytes undergo negative selection in situ, we demonstrate that phagocytosis promotes negative selection, and provide evidence for the escape of autoreactive CD8 T cells to the periphery when phagocytosis in the thymus is impaired. We also show that negative selection is more efficient when the phagocyte also presents the negative selecting peptide. Our findings support a model for negative selection in which the death process initiated following strong TCR signaling is facilitated by phagocytosis. Thus, the phagocytic capability of cells that present self-peptides is a key determinant of thymocyte fate.https://elifesciences.org/articles/48097central tolerancenegative selectionthymocytephagocytosis |
| spellingShingle | Nadia S Kurd Lydia K Lutes Jaewon Yoon Shiao Wei Chan Ivan L Dzhagalov Ashley R Hoover Ellen A Robey A role for phagocytosis in inducing cell death during thymocyte negative selection eLife central tolerance negative selection thymocyte phagocytosis |
| title | A role for phagocytosis in inducing cell death during thymocyte negative selection |
| title_full | A role for phagocytosis in inducing cell death during thymocyte negative selection |
| title_fullStr | A role for phagocytosis in inducing cell death during thymocyte negative selection |
| title_full_unstemmed | A role for phagocytosis in inducing cell death during thymocyte negative selection |
| title_short | A role for phagocytosis in inducing cell death during thymocyte negative selection |
| title_sort | role for phagocytosis in inducing cell death during thymocyte negative selection |
| topic | central tolerance negative selection thymocyte phagocytosis |
| url | https://elifesciences.org/articles/48097 |
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