TRAM deletion attenuates monocyte exhaustion and alleviates sepsis severity

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dc.contributor.authorWang, Jingen
dc.contributor.authorWu, Yajunen
dc.contributor.authorLin, Ruicien
dc.contributor.authorZhang, Yaoen
dc.contributor.authorLi, Liwuen
dc.date.accessioned2024-02-01T14:24:16Zen
dc.date.available2024-02-01T14:24:16Zen
dc.date.issued2023-12-15en
dc.description.abstractMonocyte exhaustion characterized by immune-suppressive features can develop during sepsis and contribute to adverse patient outcomes. However, molecular mechanisms responsible for the establishment of immune-suppressive monocytes with reduced expression of immune-enhancing mediators such as CD86 during sepsis are not well understood. In this study, we identified that the TLR4 intracellular adaptor TRAM plays a key role in mediating the sustained reduction of CD86 expression on exhausted monocytes and generating an immune-suppressive monocyte state. TRAM contributes to the prolonged suppression of CD86 through inducing TAX1BP1 as well as SARM1, collectively inhibiting Akt and NFκB. TRAM deficient mice are protected from cecal slurry-induced experimental sepsis and retain immune-competent monocytes with CD86 expression. Our data reveal a key molecular circuitry responsible for monocyte exhaustion and provide a viable target for rejuvenating functional monocytes and treating sepsis.en
dc.description.versionPublished versionen
dc.format.extent11 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN 1297329 (Article number)en
dc.identifier.doihttps://doi.org/10.3389/fimmu.2023.1297329en
dc.identifier.eissn1664-3224en
dc.identifier.issn1664-3224en
dc.identifier.orcidLi, Liwu [0000-0001-8870-5299]en
dc.identifier.pmid38162637en
dc.identifier.urihttps://hdl.handle.net/10919/117784en
dc.identifier.volume14en
dc.language.isoenen
dc.publisherFrontiersen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/38162637en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectmonocyte exhaustionen
dc.subjectTRAMen
dc.subjectsepsisen
dc.subjectinterventionen
dc.subjectsignalingen
dc.subject.meshMonocytesen
dc.subject.meshAnimalsen
dc.subject.meshHumansen
dc.subject.meshMiceen
dc.subject.meshSepsisen
dc.subject.meshCytoskeletal Proteinsen
dc.subject.meshArmadillo Domain Proteinsen
dc.subject.meshImmune System Exhaustionen
dc.titleTRAM deletion attenuates monocyte exhaustion and alleviates sepsis severityen
dc.title.serialFrontiers in Immunologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2023-12-04en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/Biological Sciencesen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Internal Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Internal Medicine/Secondary Appointment- Internal Medicineen
pubs.organisational-group/Virginia Tech/VT Carilion School of Medicine/Internal Medicine/Internal Med-Subgroupen

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