Biology subjects

Carroll, E. C.

Publications and source records attributed to Carroll, E. C..

2 recordsLinked to original sources

bioRxiv2019

GATA3 controls mitochondrial biogenesis in primary human CD4+ T cells during DNA damage

Introductory paragraphGATA binding protein 3 (GATA3) has traditionally been regarded as a lineage-specific transcription factor that drives the differentiation of CD4+ T helper (Th) 2 cells. However, increasing evidence shows that GATA3 is involved in a myriad of processes such as immune regulation, proliferation and maintenance in other T cell and non-T cell lineages. We show here a previously unknown mechanism utilized by CD4+ T cells to increase mitochondrial mass in response to DNA damage through the binding of GATA3, AMP-activated protein kinase (AMPK), peroxisome-proliferator-activated receptor {gamma} co-activator-1 (PGC1), nuclear factor erythroid 2-related factor 2 (NRF2) and superoxide dismutase 3 (SOD3) to the DNA damage repair (DDR) component ATR. These findings extend the pleotropic nature of GATA3 and highlight the potential for GATA3-targeted cell manipulation for clinical interventions.

immunology↗

bioRxiv2019

Mitochondrial mass governs the extent of T cell senescence

The susceptibility of human CD4+ and CD8+ T cells to senesce differs, with CD8+ T cells acquiring an immunosenescent phenotype faster than their CD4+ T cell compartment. We show here that it is the inherent difference in mitochondrial content that drives this phenotype, with senescent human CD4+ T cells displaying a higher mitochondrial mass. The loss of mitochondria in the senescent human CD8+ T cells has knock-on consequences for nutrient usage, metabolism and function. Mitochondrial dysfunction has been linked to both cellular senescence and ageing, however it is still unclear whether mitochondria play a causal role in senescence. Our data shows that reducing mitochondrial function in human CD4+ T cells, through the addition of low dose rotenone, causes the generation of a CD4+ T cell with a CD8+ -like phenotype. Therefore we wish to propose that it is the inherent metabolic stability that governs the susceptibility to an immunosenescent phenotype.

immunology↗