Details

Autor(en) / Beteiligte

• Afzal, Samia
• Hao, Zhenyue
• Itsumi, Momoe
• Abouelkheer, Yasser
• Brenner, Dirk
• Gao, Yunfei
• Wakeham, Andrew
• Hong, Claire
• Li, Wanda Y.
• Sylvester, Jennifer
• Gilani, Syed O.
• Brüstle, Anne
• Haight, Jillian
• You-Ten, Annick J.
• Lin, Gloria H. Y.
• Inoue, Satoshi
• Mak, Tak W.

Titel

Autophagy-independent functions of UVRAG are essential for peripheral naive T-cell homeostasis

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2015-01, Vol.112 (4), p.1119-1124

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2015

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 ofUvragin 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 naïve peripheral T-cell homeostasis.