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

TitleAutophagy-independent functions of UVRAG are essential for peripheral naive T-cell homeostasis
Authors
KeywordsT-cell homeostasis
UVRAG-deficient mice
Embryonic lethality
Autophagy
Issue Date2015
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?
AbstractUV 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 Identifierhttp://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 FieldValueLanguage
dc.contributor.authorAfzal, Samia-
dc.contributor.authorHao, Zhenyue-
dc.contributor.authorItsumi, Momoe-
dc.contributor.authorAbouelkheer, Yasser-
dc.contributor.authorBrenner, Dirk-
dc.contributor.authorGao, Yunfei-
dc.contributor.authorWakeham, Andrew-
dc.contributor.authorHong, Claire-
dc.contributor.authorLi, Wanda Y.-
dc.contributor.authorSylvester, Jennifer-
dc.contributor.authorGilani, Syed O.-
dc.contributor.authorBrüstle, Anne-
dc.contributor.authorHaight, Jillian-
dc.contributor.authorYou-Ten, Annick J.-
dc.contributor.authorLin, Gloria H.Y.-
dc.contributor.authorInoue, Satoshi-
dc.contributor.authorMak, Tak W.-
dc.date.accessioned2020-11-17T14:57:22Z-
dc.date.available2020-11-17T14:57:22Z-
dc.date.issued2015-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2015, v. 112, n. 4, p. 1119-1124-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/292865-
dc.description.abstractUV 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.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.subjectT-cell homeostasis-
dc.subjectUVRAG-deficient mice-
dc.subjectEmbryonic lethality-
dc.subjectAutophagy-
dc.titleAutophagy-independent functions of UVRAG are essential for peripheral naive T-cell homeostasis-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1423588112-
dc.identifier.pmid25583492-
dc.identifier.pmcidPMC4313859-
dc.identifier.scopuseid_2-s2.0-84921809383-
dc.identifier.volume112-
dc.identifier.issue4-
dc.identifier.spage1119-
dc.identifier.epage1124-
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000348417000049-
dc.identifier.issnl0027-8424-

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