| First Author | Wilfahrt D | Year | 2021 |
| Journal | Elife | Volume | 10 |
| PubMed ID | 34854376 | Mgi Jnum | J:344007 |
| Mgi Id | MGI:6833813 | Doi | 10.7554/eLife.70978 |
| Citation | Wilfahrt D, et al. (2021) Histone deacetylase 3 represses cholesterol efflux during CD4(+) T-cell activation. Elife 10:e70978 |
| abstractText | After antigenic activation, quiescent naive CD4(+) T cells alter their metabolism to proliferate. This metabolic shift increases production of nucleotides, amino acids, fatty acids, and sterols. Here, we show that histone deacetylase 3 (HDAC3) is critical for activation of murine peripheral CD4(+) T cells. HDAC3-deficient CD4(+) T cells failed to proliferate and blast after in vitro TCR/CD28 stimulation. Upon T-cell activation, genes involved in cholesterol biosynthesis are upregulated while genes that promote cholesterol efflux are repressed. HDAC3-deficient CD4(+) T cells had reduced levels of cellular cholesterol both before and after activation. HDAC3-deficient cells upregulate cholesterol synthesis appropriately after activation, but fail to repress cholesterol efflux; notably, they overexpress cholesterol efflux transporters ABCA1 and ABCG1. Repression of these genes is the primary function for HDAC3 in peripheral CD4(+) T cells, as addition of exogenous cholesterol restored proliferative capacity. Collectively, these findings demonstrate HDAC3 is essential during CD4(+) T-cell activation to repress cholesterol efflux. |
