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dc.contributor.authorSowerby, JM
dc.contributor.authorThomas, DC
dc.contributor.authorClare, S
dc.contributor.authorEspeli, M
dc.contributor.authorGuerrero, JA
dc.contributor.authorHoenderdos, K
dc.contributor.authorHarcourt, K
dc.contributor.authorMarsden, M
dc.contributor.authorAbdul-Karim, J
dc.contributor.authorClement, M
dc.contributor.authorAntrobus, R
dc.contributor.authorUmrania, Y
dc.contributor.authorBarton, PR
dc.contributor.authorFlint, SM
dc.contributor.authorJuss, JK
dc.contributor.authorCondliffe, AM
dc.contributor.authorLyons, PA
dc.contributor.authorHumphreys, IR
dc.contributor.authorChilvers, ER
dc.contributor.authorOuwehand, WH
dc.contributor.authorDougan, G
dc.contributor.authorSmith, KGC
dc.date.accessioned2020-12-21T01:42:56Z
dc.date.available2020-12-21T01:42:56Z
dc.date.issued2017-09-01
dc.identifierpii: 91684
dc.identifier.citationSowerby, J. M., Thomas, D. C., Clare, S., Espeli, M., Guerrero, J. A., Hoenderdos, K., Harcourt, K., Marsden, M., Abdul-Karim, J., Clement, M., Antrobus, R., Umrania, Y., Barton, P. R., Flint, S. M., Juss, J. K., Condliffe, A. M., Lyons, P. A., Humphreys, I. R., Chilvers, E. R. ,... Smith, K. G. C. (2017). NBEAL2 is required for neutrophil and NK cell function and pathogen defense. JOURNAL OF CLINICAL INVESTIGATION, 127 (9), pp.3259-3264. https://doi.org/10.1172/JCI91684.
dc.identifier.issn0021-9738
dc.identifier.urihttp://hdl.handle.net/11343/256628
dc.description.abstractMutations in the human NBEAL2 gene cause gray platelet syndrome (GPS), a bleeding diathesis characterized by a lack of α granules in platelets. The functions of the NBEAL2 protein have not been explored outside platelet biology, but there are reports of increased frequency of infection and abnormal neutrophil morphology in patients with GPS. We therefore investigated the role of NBEAL2 in immunity by analyzing the phenotype of Nbeal2-deficient mice. We found profound abnormalities in the Nbeal2-deficient immune system, particularly in the function of neutrophils and NK cells. Phenotyping of Nbeal2-deficient neutrophils showed a severe reduction in granule contents across all granule subsets. Despite this, Nbeal2-deficient neutrophils had an enhanced phagocyte respiratory burst relative to Nbeal2-expressing neutrophils. This respiratory burst was associated with increased expression of cytosolic components of the NADPH oxidase complex. Nbeal2-deficient NK cells were also dysfunctional and showed reduced degranulation. These abnormalities were associated with increased susceptibility to both bacterial (Staphylococcus aureus) and viral (murine CMV) infection in vivo. These results define an essential role for NBEAL2 in mammalian immunity.
dc.languageEnglish
dc.publisherAMER SOC CLINICAL INVESTIGATION INC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleNBEAL2 is required for neutrophil and NK cell function and pathogen defense
dc.typeJournal Article
dc.identifier.doi10.1172/JCI91684
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.source.titleJournal of Clinical Investigation
melbourne.source.volume127
melbourne.source.issue9
melbourne.source.pages3259-3264
dc.rights.licenseCC BY
melbourne.elementsid1227687
melbourne.contributor.authorDougan, Gordon
dc.identifier.eissn1558-8238
melbourne.accessrightsOpen Access


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