First Author | Simula L | Year | 2018 |
Journal | Cell Rep | Volume | 25 |
Issue | 11 | Pages | 3059-3073.e10 |
PubMed ID | 30540939 | Mgi Jnum | J:270811 |
Mgi Id | MGI:6278749 | Doi | 10.1016/j.celrep.2018.11.018 |
Citation | Simula L, et al. (2018) Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming. Cell Rep 25(11):3059-3073.e10 |
abstractText | 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. |