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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Reiko Hanada & Andreas Leibbrandt & Toshikatsu Hanada & Shiho Kitaoka & Tomoyuki Furuyashiki & Hiroaki Fujihara & Jean Trichereau & Magdalena Paolino & Fatimunnisa Qadri & Ralph Plehm & Steffen Klaere, 2009. "Central control of fever and female body temperature by RANKL/RANK," Nature, Nature, vol. 462(7272), pages 505-509, November.
    • Handle: RePEc:nat:nature:v:462:y:2009:i:7272:d:10.1038_nature08596
    DOI: 10.1038/nature08596
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    Cited by:

    1. Ana Sofia Rocha & Alejandro Collado-Solé & Osvaldo Graña-Castro & Jaime Redondo-Pedraza & Gonzalo Soria-Alcaide & Alex Cordero & Patricia G. Santamaría & Eva González-Suárez, 2023. "Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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