NFATc1 controls the cytotoxicity of CD8+ T cells
dc.contributor.author | Klein-Hessling, S | |
dc.contributor.author | Muhammad, K | |
dc.contributor.author | Klein, M | |
dc.contributor.author | Pusch, T | |
dc.contributor.author | Rudolf, R | |
dc.contributor.author | Flöter, J | |
dc.contributor.author | Qureischi, M | |
dc.contributor.author | Beilhack, A | |
dc.contributor.author | Vaeth, M | |
dc.contributor.author | Kummerow, C | |
dc.contributor.author | Backes, C | |
dc.contributor.author | Schoppmeyer, R | |
dc.contributor.author | Hahn, U | |
dc.contributor.author | Hoth, M | |
dc.contributor.author | Bopp, T | |
dc.contributor.author | Berberich-Siebelt, F | |
dc.contributor.author | Patra, AK | |
dc.contributor.author | Avots, A | |
dc.contributor.author | Müller, N | |
dc.contributor.author | Schulze, A | |
dc.contributor.author | Serfling, E | |
dc.date.accessioned | 2017-10-06T15:10:58Z | |
dc.date.available | 2017-10-06T15:10:58Z | |
dc.date.issued | 2017-12 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.other | 511 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/10027 | |
dc.description.abstract |
<jats:title>Abstract</jats:title><jats:p>Cytotoxic T lymphocytes are effector CD8<jats:sup>+</jats:sup> T cells that eradicate infected and malignant cells. Here we show that the transcription factor NFATc1 controls the cytotoxicity of mouse cytotoxic T lymphocytes. Activation of <jats:italic>Nfatc1</jats:italic><jats:sup> <jats:italic>−/−</jats:italic> </jats:sup> cytotoxic T lymphocytes showed a defective cytoskeleton organization and recruitment of cytosolic organelles to immunological synapses. These cells have reduced cytotoxicity against tumor cells, and mice with NFATc1-deficient T cells are defective in controlling Listeria infection. Transcriptome analysis shows diminished RNA levels of numerous genes in <jats:italic>Nfatc1</jats:italic><jats:sup> <jats:italic>−/−</jats:italic> </jats:sup> CD8<jats:sup>+</jats:sup> T cells, including <jats:italic>Tbx21</jats:italic>, <jats:italic>Gzmb</jats:italic> and genes encoding cytokines and chemokines, and genes controlling glycolysis. <jats:italic>Nfatc1</jats:italic><jats:sup> <jats:italic>−/−</jats:italic> </jats:sup>, but not <jats:italic>Nfatc2</jats:italic><jats:sup> <jats:italic>−/−</jats:italic> </jats:sup> CD8<jats:sup>+</jats:sup> T cells have an impaired metabolic switch to glycolysis, which can be restored by IL-2. Genome-wide ChIP-seq shows that NFATc1 binds many genes that control cytotoxic T lymphocyte activity. Together these data indicate that NFATc1 is an important regulator of cytotoxic T lymphocyte effector functions.</jats:p> | |
dc.format.extent | 0-0 | |
dc.format.medium | Electronic | |
dc.language | en | |
dc.language.iso | en | |
dc.publisher | Springer Science and Business Media LLC | |
dc.subject | Animals | |
dc.subject | CD8-Positive T-Lymphocytes | |
dc.subject | Cytokines | |
dc.subject | Cytoskeleton | |
dc.subject | Gene Expression Profiling | |
dc.subject | Gene Expression Regulation | |
dc.subject | Glycolysis | |
dc.subject | Granzymes | |
dc.subject | Immunological Synapses | |
dc.subject | Listeriosis | |
dc.subject | Lymphocyte Activation | |
dc.subject | Mice | |
dc.subject | Mice, Knockout | |
dc.subject | NFATC Transcription Factors | |
dc.subject | Organelles | |
dc.subject | T-Box Domain Proteins | |
dc.subject | T-Lymphocytes, Cytotoxic | |
dc.title | NFATc1 controls the cytotoxicity of CD8+ T cells | |
dc.type | journal-article | |
dc.type | Journal Article | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000410237600013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 1 | |
plymouth.volume | 8 | |
plymouth.publication-status | Published online | |
plymouth.journal | Nature Communications | |
dc.identifier.doi | 10.1038/s41467-017-00612-6 | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/Faculty of Health/Peninsula Medical School | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/Users by role | |
plymouth.organisational-group | /Plymouth/Users by role/Academics | |
dc.publisher.place | England | |
dcterms.dateAccepted | 2017-07-09 | |
dc.identifier.eissn | 2041-1723 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1038/s41467-017-00612-6 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2017-12 | |
rioxxterms.type | Journal Article/Review |