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

Reiko Hanada, Andreas Leibbrandt, Toshikatsu Hanada, Shiho Kitaoka, Tomoyuki Furuyashiki, Hiroaki Fujihara, Jean Trichereau, Magdalena Paolino, Fatimunnisa Qadri, Ralph Plehm, Steffen Klaere, Vukoslav Komnenovic, Hiromitsu Mimata, Hironobu Yoshimatsu, Naoyuki Takahashi, Arndt von Haeseler, Michael Bader, Sara Sebnem Kilic, Yoichi Ueta, Christian Pifl, Shuh Narumiya and Josef M. Penninger ()
Additional contact information
Reiko Hanada: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences
Andreas Leibbrandt: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences
Toshikatsu Hanada: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences
Shiho Kitaoka: Kyoto University Graduate School of Medicine
Tomoyuki Furuyashiki: Kyoto University Graduate School of Medicine
Hiroaki Fujihara: School of Medicine, University of Occupational and Environmental Health
Jean Trichereau: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences
Magdalena Paolino: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences
Fatimunnisa Qadri: Max Delbrueck Centre for Molecular Medicine
Ralph Plehm: Max Delbrueck Centre for Molecular Medicine
Steffen Klaere: Center of Integrated Bioinformatics, Max F. Perutz Laboratories
Vukoslav Komnenovic: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences
Hiromitsu Mimata: Oita University Faculty of Medicine
Hironobu Yoshimatsu: Oita University Faculty of Medicine
Naoyuki Takahashi: Institute for Oral Science, Matsumoto Dental University
Arndt von Haeseler: Center of Integrated Bioinformatics, Max F. Perutz Laboratories
Michael Bader: Max Delbrueck Centre for Molecular Medicine
Sara Sebnem Kilic: Uludag University Medical Faculty
Yoichi Ueta: School of Medicine, University of Occupational and Environmental Health
Christian Pifl: Medical University of Vienna, Center for Brain Research
Shuh Narumiya: Kyoto University Graduate School of Medicine
Josef M. Penninger: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences

Nature, 2009, vol. 462, issue 7272, 505-509

Abstract: Bone protein link to fever The protein RANK (receptor-activator of nuclear factor κB) and its ligand RANKL are essential bone marrow regulators, and antibodies against RANKL are being developed as therapeutics in osteoporosis. RANKL and RANK are also expressed in the central nervous system, though their function there has been unclear. Studies in rats and mice now show that RANKL/RANK are expressed in astrocytes in the brain and that surprisingly, animals injected with RANKL develop severe fever, whereas genetically engineered mice with astrocytes lacking RANK are fever-resistant. Other data are consistent with a role for RANKL/RANK in both the central fever response in inflammation and in the control of female body temperature. Interestingly, clinical observations of two children with osteoporosis associated with RANK mutations revealed an absence of fever during bouts of pneumonia. It is possible that RANKL/RANK are factors in the hot flashes or flushes sometimes experienced by women during the menopause.

Date: 2009
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DOI: 10.1038/nature08596

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