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. 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.

Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming / 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. - In: CELL REPORTS. - ISSN 2211-1247. - 25:11(2018), pp. 3059-3073.e10. [10.1016/j.celrep.2018.11.018]

Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming

Pacella, Ilenia
Secondo
;
Barnaba, Vincenzo;Matarese, Giuseppe;Piconese, Silvia
Penultimo
;
2018

Abstract

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. 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.
2018
cell migration; cell proliferation; cMyc; Drp1; exhaustion; metabolic reprogramming; mitochondrial dynamics; T cells; thymocytes; tumor immune-surveillance; Biochemistry, Genetics and Molecular Biology (all)
01 Pubblicazione su rivista::01a Articolo in rivista
Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming / 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. - In: CELL REPORTS. - ISSN 2211-1247. - 25:11(2018), pp. 3059-3073.e10. [10.1016/j.celrep.2018.11.018]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1242240
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