We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
GATA3 induces mitochondrial biogenesis in primary human CD4+ T cells during DNA damage.
- Authors
Callender, Lauren A.; Schroth, Johannes; Carroll, Elizabeth C.; Garrod-Ketchley, Conor; Romano, Lisa E. L.; Hendy, Eleanor; Kelly, Audrey; Lavender, Paul; Akbar, Arne N.; Chapple, J. Paul; Henson, Sian M.
- Abstract
GATA3 is as a lineage-specific transcription factor that drives the differentiation of CD4+ T helper 2 (Th2) cells, but is also involved in a variety of processes such as immune regulation, proliferation and maintenance in other T cell and non-T cell lineages. Here we show a mechanism utilised by CD4+ T cells to increase mitochondrial mass in response to DNA damage through the actions of GATA3 and AMPK. Activated AMPK increases expression of PPARG coactivator 1 alpha (PPARGC1A or PGC1α protein) at the level of transcription and GATA3 at the level of translation, while DNA damage enhances expression of nuclear factor erythroid 2-related factor 2 (NFE2L2 or NRF2). PGC1α, GATA3 and NRF2 complex together with the ATR to promote mitochondrial biogenesis. These findings extend the pleotropic interactions of GATA3 and highlight the potential for GATA3-targeted cell manipulation for intervention in CD4+ T cell viability and function after DNA damage. GATA3 has been considered to be primarily associated with CD4+ Th2 cell function. Using CD4+ effector memory that re-express CD45RA (EMRA) T cells the authors show that in response to DNA damage GATA3 can regulate increase of mitochondrial mass and biogenesis involving AMPK.
- Subjects
DNA damage; T cells; CELL physiology; MITOCHONDRIA; TH2 cells
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-23715-7