Please use this identifier to cite or link to this item: http://hdl.handle.net/11452/25990
Title: Central control of fever and female body temperature by RANKL/RANK
Authors: Hanada, Reiko
Leibbrandt, Andreas
Hanada, Toshikatsu
Kitaoka, Shiho
Furuyashiki, Tomoyuki
Fujihara, Hiroaki
Trichereau, Jean
Paolino, Magdalena
Qadri, Fatimunnisa
Plehm, Ralph
Klaere, Steffen
Komnenovic, Vukoslav
Mimata, Hiromitsu
Yoshimatsu, Hironobu
Takahashi, Naoyuki
Von Haeseler, Arndt
Bader, Michael
Ueta, Yoichi
Pifl, Christian
Narumiya, Shuh
Penninger, Josef M.
Uludağ Üniversitesi/Tıp Fakültesi/Pediatrik İmmünoloji Anabilim Dalı.
0000-0001-8571-2581
Kılıç, Sara Şebnem
AAH-1658-2021
34975059200
Keywords: Osteoclast differentiation factor
Febrile response
Mice lacking
C-fos
Receptor
Inflammation
Mechanisms
Denosumab
Protein
Ligand
Science & technology - other topics
Mus
Rattus
Body temperature
Bone
Brain
Female
Ligand
Mutation
Polysaccharide
Protein
Rodent
Thermoregulation
Tumor
Issue Date: 26-Nov-2009
Publisher: Nature Research
Citation: Hanada, R. vd. (2009). "Central control of fever and female body temperature by RANKL/RANK". Nature, 462(7272), 505-509.
Abstract: Receptor-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.
URI: https://doi.org/10.1038/nature08596
https://www.nature.com/articles/nature08596
http://hdl.handle.net/11452/25990
ISSN: 0028-0836
Appears in Collections:Web of Science

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