イツミ　モモエ   逸見　百江    所属   川崎医科大学  医学部 一般教養　自然科学    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Autophagy-independent functions of UVRAG are essential for peripheral naive T-cell homeostasis.
掲載誌名	正式名：Proceedings of the National Academy of Sciences of the United States of America 略　 称：Proc Natl Acad Sci U S A ISSNコード：10916490/00278424
掲載区分	国外
巻・号・頁	112(4),pp.1119-24
著者・共著者	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
発行年月	2015/01
概要	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.
DOI	10.1073/pnas.1423588112
PMID	25583492