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

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

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)


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 naïve peripheral T-cell homeostasis.

Original languageEnglish
Pages (from-to)1119-1124
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number4
Publication statusPublished - 27 Jan 2015


  • Autophagy
  • Embryonic lethality
  • T-cell homeostasis
  • UVRAG-deficient mice


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