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dc.contributor.authorKumar, Laliten_US
dc.contributor.authorChou, Janeten_US
dc.contributor.authorYee, Christina S.K.en_US
dc.contributor.authorBorzutzky, Arturoen_US
dc.contributor.authorVollmann, Elisabeth H.en_US
dc.contributor.authorvon Andrian, Ulrich H.en_US
dc.contributor.authorPark, Shin-Youngen_US
dc.contributor.authorHollander, Georgen_US
dc.contributor.authorManis, John P.en_US
dc.contributor.authorPoliani, P. Luigien_US
dc.contributor.authorGeha, Raif S.en_US
dc.date.accessioned2014-12-02T21:28:22Z
dc.date.issued2014en_US
dc.identifier.citationKumar, L., J. Chou, C. S. Yee, A. Borzutzky, E. H. Vollmann, U. H. von Andrian, S. Park, et al. 2014. “Leucine-rich repeat containing 8A (LRRC8A) is essential for T lymphocyte development and function.” The Journal of Experimental Medicine 211 (5): 929-942. doi:10.1084/jem.20131379. http://dx.doi.org/10.1084/jem.20131379.en
dc.identifier.issn0022-1007en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13454721
dc.description.abstractLrrc8a is a ubiquitously expressed gene that encodes a leucine-rich repeat (LRR)–containing protein detected at higher levels on the surface of thymocytes than on other immune cells. We generated Lrrc8a−/− mice to investigate the role of LRRC8A in lymphocyte development and function. Lrrc8a−/− mice had increased prenatal and postnatal mortality, growth retardation, and multiple tissue abnormalities. Lrrc8a−/− mice displayed a modest block in B cell development but intact intrinsic B cell function. In contrast, both Lrrc8a−/− mice and Lrrc8a−/−→Rag2−/− bone marrow chimeras exhibited a severe cell-intrinsic block in early thymic development, with decreased proliferation and increased apoptosis of thymocytes, and impaired peripheral T cell function. Thymic epithelial cells expressed an LRRC8A ligand that was critical for double-negative to double-positive thymocyte differentiation and survival in vitro. LRRC8A constitutively associated with the GRB2–GAB2 complex and lymphocyte-specific protein tyrosine kinase (LCK) in thymocytes. LRRC8A ligation activated AKT via the LCK–ZAP–70–GAB2–PI3K pathway, and AKT phosphorylation was markedly reduced in the thymus of Lrrc8a−/− mice. These findings reveal an essential role for LRRC8A in T cell development, survival, and function.en
dc.language.isoen_USen
dc.publisherThe Rockefeller University Pressen
dc.relation.isversionofdoi:10.1084/jem.20131379en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010910/pdf/en
dash.licenseLAAen_US
dc.titleLeucine-rich repeat containing 8A (LRRC8A) is essential for T lymphocyte development and functionen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalThe Journal of Experimental Medicineen
dash.depositing.authorKumar, Laliten_US
dc.date.available2014-12-02T21:28:22Z
dc.identifier.doi10.1084/jem.20131379*
dash.authorsorderedfalse
dash.contributor.affiliatedGeha, Raif
dash.contributor.affiliatedPark, Shin-Young
dash.contributor.affiliatedVollmann, Elisabeth H.
dash.contributor.affiliatedBorzutzky, Arturo
dash.contributor.affiliatedKumar, Lalit
dash.contributor.affiliatedChou, Janet
dash.contributor.affiliatedYee, Christina
dash.contributor.affiliatedvon Andrian-Werburg, Ulrich
dash.contributor.affiliatedManis, John


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