Chaperone-mediated autophagy regulates T cell responses through targeted degradation of negative regulators of T cell activation
| العنوان: | Chaperone-mediated autophagy regulates T cell responses through targeted degradation of negative regulators of T cell activation |
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| المؤلفون: | Ignacio Guerrero-Ros, Fernando Macian, Dinesh Chandra, Yair Botbol, Ana Maria Cuervo, Enric Mocholi, Hiroshi Koga, Claudia Gravekamp, Rut Valdor |
| المصدر: | Nature immunology |
| بيانات النشر: | Springer Science and Business Media LLC, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Aging, Muscle Proteins, Basic helix-loop-helix leucine zipper transcription factors, Lymphocyte Activation, Mice, 0302 clinical medicine, Chaperone-mediated autophagy, RNA interference, Immunology and Allergy, Listeriosis, RNA, Small Interfering, health care economics and organizations, Cells, Cultured, Mice, Knockout, 0303 health sciences, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Intracellular Signaling Peptides and Proteins, Dual Oxidases, humanities, Cell biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, RNA Interference, Ubiquitin-Protein Ligases, T cell, Calcineurin Inhibitors, Immunology, Receptors, Antigen, T-Cell, Biology, Article, 03 medical and health sciences, Lysosomal-Associated Membrane Protein 2, Autophagy, medicine, Animals, Humans, RNA, Messenger, 030304 developmental biology, Calcium-Binding Proteins, T-cell receptor, NADPH Oxidases, Th1 Cells, Listeria monocytogenes, Mice, Inbred C57BL, Calcineurin, Oxidative Stress, Cytoplasm, Immunization, Reactive Oxygen Species, Molecular Chaperones |
| الوصف: | Chaperone-mediated autophagy (CMA) targets soluble proteins for lysosomal degradation. Here we found that CMA was activated in T cells in response to engagement of the T cell antigen receptor (TCR), which induced expression of the CMA-related lysosomal receptor LAMP-2A. In activated T cells, CMA targeted the ubiquitin ligase Itch and the calcineurin inhibitor RCAN1 for degradation to maintain activation-induced responses. Consequently, deletion of the gene encoding LAMP-2A in T cells caused deficient in vivo responses to immunization or infection with Listeria monocytogenes. Impaired CMA activity also occurred in T cells with age, which negatively affected their function. Restoration of LAMP-2A in T cells from old mice resulted in enhancement of activation-induced responses. Our findings define a role for CMA in regulating T cell activation through the targeted degradation of negative regulators of T cell activation. |
| تدمد: | 1529-2916 1529-2908 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::78af166c1f184bdfacbb4a4b093ed990Test https://doi.org/10.1038/ni.3003Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....78af166c1f184bdfacbb4a4b093ed990 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15292916 15292908 |
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