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- Publisher Website: 10.1073/pnas.1423588112
- Scopus: eid_2-s2.0-84921809383
- PMID: 25583492
- WOS: WOS:000348417000049
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Article: Autophagy-independent functions of UVRAG are essential for peripheral naive T-cell homeostasis
Title | Autophagy-independent functions of UVRAG are essential for peripheral naive T-cell homeostasis |
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Authors | |
Keywords | T-cell homeostasis UVRAG-deficient mice Embryonic lethality Autophagy |
Issue Date | 2015 |
Citation | Proceedings of the National Academy of Sciences of the United States of America, 2015, v. 112, n. 4, p. 1119-1124 How to Cite? |
Abstract | 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. |
Persistent Identifier | http://hdl.handle.net/10722/292865 |
ISSN | 2023 Impact Factor: 9.4 2023 SCImago Journal Rankings: 3.737 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Afzal, Samia | - |
dc.contributor.author | Hao, Zhenyue | - |
dc.contributor.author | Itsumi, Momoe | - |
dc.contributor.author | Abouelkheer, Yasser | - |
dc.contributor.author | Brenner, Dirk | - |
dc.contributor.author | Gao, Yunfei | - |
dc.contributor.author | Wakeham, Andrew | - |
dc.contributor.author | Hong, Claire | - |
dc.contributor.author | Li, Wanda Y. | - |
dc.contributor.author | Sylvester, Jennifer | - |
dc.contributor.author | Gilani, Syed O. | - |
dc.contributor.author | Brüstle, Anne | - |
dc.contributor.author | Haight, Jillian | - |
dc.contributor.author | You-Ten, Annick J. | - |
dc.contributor.author | Lin, Gloria H.Y. | - |
dc.contributor.author | Inoue, Satoshi | - |
dc.contributor.author | Mak, Tak W. | - |
dc.date.accessioned | 2020-11-17T14:57:22Z | - |
dc.date.available | 2020-11-17T14:57:22Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America, 2015, v. 112, n. 4, p. 1119-1124 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10722/292865 | - |
dc.description.abstract | 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. | - |
dc.language | eng | - |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.subject | T-cell homeostasis | - |
dc.subject | UVRAG-deficient mice | - |
dc.subject | Embryonic lethality | - |
dc.subject | Autophagy | - |
dc.title | Autophagy-independent functions of UVRAG are essential for peripheral naive T-cell homeostasis | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1073/pnas.1423588112 | - |
dc.identifier.pmid | 25583492 | - |
dc.identifier.pmcid | PMC4313859 | - |
dc.identifier.scopus | eid_2-s2.0-84921809383 | - |
dc.identifier.volume | 112 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 1119 | - |
dc.identifier.epage | 1124 | - |
dc.identifier.eissn | 1091-6490 | - |
dc.identifier.isi | WOS:000348417000049 | - |
dc.identifier.issnl | 0027-8424 | - |