Autophagy-independent functions of UVRAG are essential for peripheral naive T-cell homeostasis.
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 112 (2015-01-27), Heft 4, S. 1119-1124
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Zugriff:
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 UVRAGdeficient 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. [ABSTRACT FROM AUTHOR]
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Autophagy-independent functions of UVRAG are essential for peripheral naive T-cell homeostasis.
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Autor/in / Beteiligte Person: | 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. |
Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 112 (2015-01-27), Heft 4, S. 1119-1124 |
Veröffentlichung: | 2015 |
Medientyp: | academicJournal |
ISSN: | 0027-8424 (print) |
DOI: | 10.1073/pnas.1423588112 |
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