Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming
| العنوان: | Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming |
|---|---|
| المؤلفون: | Matteo Bordi, Valeria Cancila, Alessandra Colamatteo, Silvia Campello, Mauro Corrado, Silvia Piconese, Claudio Procaccini, Ilenia Pacella, Luca Simula, Claudio Tripodo, Vincenzo Barnaba, Martina Pigazzi, Claudia Tregnago, Giuseppe Matarese |
| المساهمون: | Simula L., Pacella I., Colamatteo A., Procaccini C., Cancila V., Bordi M., Tregnago C., Corrado M., Pigazzi M., Barnaba V., Tripodo C., Matarese G., Piconese S., Campello S., Simula, Luca, Pacella, Ilenia, Colamatteo, Alessandra, Procaccini, Claudio, Cancila, Valeria, Bordi, Matteo, Tregnago, Claudia, Corrado, Mauro, Pigazzi, Martina, Barnaba, Vincenzo, Tripodo, Claudio, Matarese, Giuseppe, Piconese, Silvia, Campello, Silvia |
| المصدر: | Cell Reports Cell Reports, Vol 25, Iss 11, Pp 3059-3073.e10 (2018) Cell reports 25 (2018): 3059–3073.e10. doi:10.1016/j.celrep.2018.11.018 info:cnr-pdr/source/autori:Simula L.; Pacella I.; Colamatteo A.; Procaccini C.; Cancila V.; Bordi M.; Tregnago C.; Corrado M.; Pigazzi M.; Barnaba V.; Tripodo C.; Matarese G.; Piconese S.; Campello S./titolo:Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming/doi:10.1016%2Fj.celrep.2018.11.018/rivista:Cell reports/anno:2018/pagina_da:3059/pagina_a:3073.e10/intervallo_pagine:3059–3073.e10/volume:25 |
| بيانات النشر: | Elsevier B.V., 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Genetics and Molecular Biology (all), 0301 basic medicine, cell migration, T-Lymphocytes, Cell, Cell Count, Mitochondrion, Lymphocyte Activation, Biochemistry, Cell Movement, Homeostasis, metabolic reprogramming, cell proliferation, cMyc, Drp1, exhaustion, mitochondrial dynamics, T cells, thymocytes, tumor immune-surveillance, Biochemistry, Genetics and Molecular Biology (all), lcsh:QH301-705.5, Immunologic Surveillance, Mice, Knockout, Thymocytes, Effector, Cell migration, Cell Differentiation, Cell biology, medicine.anatomical_structure, Phenotype, Dynamins, endocrine system, Settore BIO/06, Cell Survival, Lymphoid Tissue, MAP Kinase Signaling System, T cell, Receptors, Antigen, T-Cell, Biology, General Biochemistry, Genetics and Molecular Biology, Article, Proto-Oncogene Proteins c-myc, 03 medical and health sciences, mitochondrial dynamic, Homeostasi, medicine, Animals, Cell Proliferation, Tumor microenvironment, Cell growth, Animal, thymocyte, Dynamin, 030104 developmental biology, lcsh:Biology (General), T-Lymphocyte, T cell migration |
| الوصف: | Summary Mitochondria are key players in the regulation of T cell biology by dynamically responding to cell needs, but how these dynamics integrate in T cells is still poorly understood. We show here that the mitochondrial pro-fission protein Drp1 fosters migration and expansion of developing thymocytes both in vitro and in vivo. In addition, we find that Drp1 sustains in vitro clonal expansion and cMyc-dependent metabolic reprogramming upon activation, also regulating effector T cell numbers in vivo. Migration and extravasation defects are also exhibited in Drp1-deficient mature T cells, unveiling its crucial role in controlling both T cell recirculation in secondary lymphoid organs and accumulation at tumor sites. Moreover, the observed Drp1-dependent imbalance toward a memory-like phenotype favors T cell exhaustion in the tumor microenvironment. All of these findings support a crucial role for Drp1 in several processes during T cell development and in anti-tumor immune-surveillance. Graphical Abstract Highlights • The pro-fission protein Drp1 sustains correct thymocyte maturation • Drp1 promotes T cell metabolic reprogramming and expansion upon activation • Drp1 allows efficient T cell extravasation from blood and infiltration into tumors • An optimal T cell anti-tumor response requires Drp1 Mitochondria are emerging as key players for optimal T cell functionality. Simula et al. demonstrate that the mitochondrial pro-fission factor Drp1 controls thymocyte maturation and plays multiple roles in mature T cells by promoting their proliferation, migration, and cMyc-dependent metabolic reprogramming upon activation; this activity sustains efficient anti-tumor immune-surveillance. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a53685732c50cbef638aa82681525489Test http://hdl.handle.net/10447/395012Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a53685732c50cbef638aa82681525489 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |