Central control of fever and female body temperature by RANKL/RANK

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dc.contributor.authorHanada, Reiko
dc.contributor.authorLeibbrandt, Andreas
dc.contributor.authorHanada, Toshikatsu
dc.contributor.authorKitaoka, Shiho
dc.contributor.authorFuruyashiki, Tomoyuki
dc.contributor.authorFujihara, Hiroaki
dc.contributor.authorTrichereau, Jean
dc.contributor.authorPaolino, Magdalena
dc.contributor.authorQadri, Fatimunnisa
dc.contributor.authorPlehm, Ralph
dc.contributor.authorKlaere, Steffen
dc.contributor.authorKomnenovic, Vukoslav
dc.contributor.authorMimata, Hiromitsu
dc.contributor.authorYoshimatsu, Hironobu
dc.contributor.authorTakahashi, Naoyuki
dc.contributor.authorVon Haeseler, Arndt
dc.contributor.authorBader, Michael
dc.contributor.authorUeta, Yoichi
dc.contributor.authorPifl, Christian
dc.contributor.authorNarumiya, Shuh
dc.contributor.authorPenninger, Josef M.
dc.contributor.buuauthorKılıç, Sara Şebnem
dc.contributor.departmentUludağ Üniversitesi/Tıp Fakültesi/Pediatrik İmmünoloji Anabilim Dalı.tr_TR
dc.contributor.orcid0000-0001-8571-2581tr_TR
dc.contributor.researcheridAAH-1658-2021tr_TR
dc.contributor.scopusid34975059200tr_TR
dc.date.accessioned2022-04-22T06:40:14Z
dc.date.available2022-04-22T06:40:14Z
dc.date.issued2009-11-26
dc.description.abstractReceptor-activator of NF-kappa B ligand (TNFSF11, also known as RANKL, OPGL, TRANCE and ODF) and its tumour necrosis factor (TNF)-family receptor RANK are essential regulators of bone remodelling, lymph node organogenesis and formation of a lactating mammary gland(1-4). RANKL and RANK are also expressed in the central nervous system(5,6). However, the functional relevance of RANKL/RANK in the brain was entirely unknown. Here we report that RANKL and RANK have an essential role in the brain. In both mice and rats, central RANKL injections trigger severe fever. Using tissue-specific Nestin-Cre and GFAP-Cre rank(floxed) deleter mice, the function of RANK in the fever response was genetically mapped to astrocytes. Importantly, Nestin-Cre and GFAP-Cre rank(floxed) deleter mice are resistant to lipopolysaccharide-induced fever as well as fever in response to the key inflammatory cytokines IL-1 beta and TNF alpha. Mechanistically, RANKL activates brain regions involved in thermoregulation and induces fever via the COX2-PGE(2)/EP3R pathway. Moreover, female Nestin-Cre and GFAP-Cre rank(floxed) mice exhibit increased basal body temperatures, suggesting that RANKL and RANK control thermoregulation during normal female physiology. We also show that two children with RANK mutations exhibit impaired fever during pneumonia. These data identify an entirely novel and unexpected function for the key osteoclast differentiation factors RANKL/RANK in female thermoregulation and the central fever response in inflammation.en_US
dc.description.sponsorshipAustrian Ministry of Sciencesen_US
dc.description.sponsorshipAustrian Academy of Sciencesen_US
dc.description.sponsorshipGEN-AU ( AustroMouse)en_US
dc.description.sponsorshipEuropean Commissionen_US
dc.description.sponsorshipEuropean Research Council (ERC) European Commissionen_US
dc.description.sponsorshipUehara Memorial Foundationen_US
dc.description.sponsorshipJapan Foundation for Applied Enzymologyen_US
dc.description.sponsorshipAustrian Ministry for Science and Researchen_US
dc.description.sponsorshipWiener Wissenschafts-, Forschungs- und Technologiefonds (WWTF)en_US
dc.description.sponsorshipIMBAen_US
dc.identifier.citationHanada, R. vd. (2009). "Central control of fever and female body temperature by RANKL/RANK". Nature, 462(7272), 505-509.en_US
dc.identifier.endpage509tr_TR
dc.identifier.issn0028-0836
dc.identifier.issue7272tr_TR
dc.identifier.pubmed19940926tr_TR
dc.identifier.scopus2-s2.0-70849096810tr_TR
dc.identifier.startpage505tr_TR
dc.identifier.urihttps://doi.org/10.1038/nature08596
dc.identifier.urihttps://www.nature.com/articles/nature08596
dc.identifier.urihttp://hdl.handle.net/11452/25990
dc.identifier.volume462tr_TR
dc.identifier.wos000272144200044tr_TR
dc.indexed.pubmedPubMeden_US
dc.indexed.scopusScopusen_US
dc.indexed.wosSCIEen_US
dc.language.isoenen_US
dc.publisherNature Researchen_US
dc.relation.collaborationYurt dışıtr_TR
dc.relation.journalNatureen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergitr_TR
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectOsteoclast differentiation factoren_US
dc.subjectFebrile responseen_US
dc.subjectMice lackingen_US
dc.subjectC-fosen_US
dc.subjectReceptoren_US
dc.subjectInflammationen_US
dc.subjectMechanismsen_US
dc.subjectDenosumaben_US
dc.subjectProteinen_US
dc.subjectLiganden_US
dc.subjectScience & technology - other topicsen_US
dc.subjectMusen_US
dc.subjectRattusen_US
dc.subjectBody temperatureen_US
dc.subjectBoneen_US
dc.subjectBrainen_US
dc.subjectFemaleen_US
dc.subjectLiganden_US
dc.subjectMutationen_US
dc.subjectPolysaccharideen_US
dc.subjectProteinen_US
dc.subjectRodenten_US
dc.subjectThermoregulationen_US
dc.subjectTumoren_US
dc.subject.emtreeCre recombinaseen_US
dc.subject.emtreeCyclooxygenase 2en_US
dc.subject.emtreeGlial fibrillary acidic proteinen_US
dc.subject.emtreeInterleukin 1betaen_US
dc.subject.emtreeNestinen_US
dc.subject.emtreeOsteoclast differentiation factoren_US
dc.subject.emtreeProstaglandin E2en_US
dc.subject.emtreeReceptor activator of nuclear factor kappa Ben_US
dc.subject.emtreeTumor necrosis factor alphaen_US
dc.subject.emtreeAnimal experimenten_US
dc.subject.emtreeAnimal modelen_US
dc.subject.emtreeArticleen_US
dc.subject.emtreeBody temperatureen_US
dc.subject.emtreeControlled studyen_US
dc.subject.emtreeEnzyme activationen_US
dc.subject.emtreeFemaleen_US
dc.subject.emtreeFeveren_US
dc.subject.emtreeGene mutationen_US
dc.subject.emtreeMouseen_US
dc.subject.emtreeNonhumanen_US
dc.subject.emtreePneumoniaen_US
dc.subject.emtreePriority journalen_US
dc.subject.emtreeProtein functionen_US
dc.subject.emtreeRaten_US
dc.subject.emtreeThermoregulationen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAstrocytesen_US
dc.subject.meshBody temperature regulationen_US
dc.subject.meshChilden_US
dc.subject.meshDinoprostoneen_US
dc.subject.meshFemaleen_US
dc.subject.meshFeveren_US
dc.subject.meshGene expression profilingen_US
dc.subject.meshHumansen_US
dc.subject.meshInjections, intraventricularen_US
dc.subject.meshMaleen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, inbred C57BLen_US
dc.subject.meshPneumoniaen_US
dc.subject.meshRANK liganden_US
dc.subject.meshRatsen_US
dc.subject.meshRats, wistaren_US
dc.subject.meshReceptor activator of nuclear factor-kappa Ben_US
dc.subject.meshReceptors, prostaglandin Een_US
dc.subject.meshSex characteristicsen_US
dc.subject.scopusOsteoprotegerin; Osteoclast Differentiation Factor; Ligandsen_US
dc.subject.wosMultidisciplinary sciencesen_US
dc.titleCentral control of fever and female body temperature by RANKL/RANKen_US
dc.typeArticle
dc.wos.quartileQ1en_US

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