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

Luca Simula, Ilenia Pacella, Alessandra Colamatteo, Claudio Procaccini, Valeria Cancila, Matteo Bordi, Claudia Tregnago, Mauro Corrado, Martina Pigazzi, Vincenzo Barnaba, Claudio Tripodo, Giuseppe Matarese, Silvia Piconese, Silvia Campello

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3059-3073.e10
JournalCell Reports
Volume25
Issue number11
DOIs
Publication statusPublished - Dec 11 2018

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T-cells
Cell Movement
Cell Proliferation
T-Lymphocytes
Tumors
Mitochondrial Dynamics
Mitochondria
Thymocytes
Chemical activation
Cytology
Neoplasms
Tumor Microenvironment
Cell Biology
Cell Count
Phenotype
Data storage equipment
Defects

Keywords

  • cell migration
  • cell proliferation
  • cMyc
  • Drp1
  • exhaustion
  • metabolic reprogramming
  • mitochondrial dynamics
  • T cells
  • thymocytes
  • tumor immune-surveillance

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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, Vol. 25, No. 11, 11.12.2018, p. 3059-3073.e10.

Research output: Contribution to journalArticle

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 2018, 'Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming', Cell Reports, vol. 25, no. 11, pp. 3059-3073.e10. https://doi.org/10.1016/j.celrep.2018.11.018
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. / Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming. In: Cell Reports. 2018 ; Vol. 25, No. 11. pp. 3059-3073.e10.
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