| First Author | Afzal S | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 4 | Pages | 1119-24 |
| PubMed ID | 25583492 | Mgi Jnum | J:219272 |
| Mgi Id | MGI:5620044 | Doi | 10.1073/pnas.1423588112 |
| Citation | Afzal S, et al. (2015) Autophagy-independent functions of UVRAG are essential for peripheral naive T-cell homeostasis. Proc Natl Acad Sci U S A 112(4):1119-24 |
| abstractText | UV radiation resistance-associated gene (UVRAG) encodes a tumor suppressor with putative roles in autophagy, endocytic trafficking, and DNA damage repair but its in vivo role in T cells is unknown. Because conditional homozygous deletion of Uvrag in mice results in early embryonic lethality, we generated T-cell-specific UVRAG-deficient mice that lacked UVRAG expression specifically in T cells. This loss of UVRAG led to defects in peripheral homeostasis that could not be explained by the increased sensitivity to cell death and impaired proliferation observed for other autophagy-related gene knockout mice. Instead, UVRAG-deficient T-cells exhibited normal mitochondrial clearance and activation-induced autophagy, suggesting that UVRAG has an autophagy-independent role that is critical for peripheral naive T-cell homeostatic proliferation. In vivo, T-cell-specific loss of UVRAG dampened CD8(+) T-cell responses to LCMV infection in mice, delayed viral clearance, and impaired memory T-cell generation. Our data provide novel insights into the control of autophagy in T cells and identify UVRAG as a new regulator of naive peripheral T-cell homeostasis. |
