Restricted Expression of the Thymoproteasome Is Required for Thymic Selection and Peripheral Homeostasis of CD8
| Autor: | Rikuto Kimoto, Shizuka Kiuchi, Akihiro Ishizu, Saori Konno, Syota Miyajima, Mari Onodera, Utano Tomaru, Masanori Kasahara, Shigeo Murata |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Proteasome Endopeptidase Complex Lineage (genetic) Protein subunit autoimmune disease Biology CD8-Positive T-Lymphocytes medicine.disease_cause General Biochemistry Genetics and Molecular Biology Autoimmunity 03 medical and health sciences Mice 0302 clinical medicine thymoproteasome memory T cells medicine Cytotoxic T cell Animals Homeostasis Humans Medulla naïve T cells Thymocytes autoimmunity Phenotype Cell biology 030104 developmental biology proteasome thymic selection thymic epithelial cells self peptide 030217 neurology & neurosurgery CD8 |
| Zdroj: | Cell reports. 26(3) |
| ISSN: | 2211-1247 |
| Popis: | Summary The thymoproteasome subunit β5t is specifically expressed in cortical thymic epithelial cells (TECs) and generates unique peptides to support positive selection. In this study, using a mouse model ubiquitously expressing β5t, we showed that aberrant expression of self-peptides generated by β5t affects CD8+ T cell homeostasis, including thymic selection and maintenance of the peripheral naive pool of CD8+ T cells. In mice in which β5t was expressed both in cortical and medullary TECs, the abundance of CD8+ lineage thymocytes was reduced, and extra-thymic expression of β5t caused accumulation of CD8+ T cells with the memory or exhausted phenotype and induced autoreactive T cell responses. We found that thymoproteasomes are essential for positive selection but that the subsequent change in peptide repertoire in the medulla is also crucial for thymic selection and that β5t-derived peptide must be confined to the thymus to avoid autoimmunity in peripheral tissues. |
| Databáze: | OpenAIRE |
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