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VALERIA CANCILA

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

  • 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.
  • Anno di pubblicazione: 2018
  • Tipologia: Articolo in rivista
  • OA Link: http://hdl.handle.net/10447/395012

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.