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Epidermal phospholipase Cδ1 regulates granulocyte counts and systemic interleukin-17 levels in mice

Author

Listed:
  • Kaori Kanemaru

    (Laboratory of Genome and Biosignal, Tokyo University of Pharmacy and Life Sciences)

  • Yoshikazu Nakamura

    (Laboratory of Genome and Biosignal, Tokyo University of Pharmacy and Life Sciences)

  • Kojiro Sato

    (Faculty of Medicine, Saitama Medical University)

  • Ryota Kojima

    (Laboratory of Genome and Biosignal, Tokyo University of Pharmacy and Life Sciences)

  • Saori Takahashi

    (Laboratory of Genome and Biosignal, Tokyo University of Pharmacy and Life Sciences)

  • Mami Yamaguchi

    (Laboratory of Genome and Biosignal, Tokyo University of Pharmacy and Life Sciences)

  • Manabu Ichinohe

    (Laboratory of Genome and Biosignal, Tokyo University of Pharmacy and Life Sciences)

  • Hiroshi Kiyonari

    (Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology)

  • Go Shioi

    (Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology)

  • Kenji Kabashima

    (Graduate School of Medicine, Kyoto University)

  • Kyoko Nakahigashi

    (Graduate School of Medicine, Kyoto University)

  • Masataka Asagiri

    (University of California San Diego
    Innovation Center for Immunoregulation and Therapeutics, Graduate School of Medicine, Kyoto University)

  • Colin Jamora

    (Section of Cell and Developmental Biology, University of California San Diego)

  • Hideki Yamaguchi

    (National Cancer Center Research Institute)

  • Kiyoko Fukami

    (Laboratory of Genome and Biosignal, Tokyo University of Pharmacy and Life Sciences)

Abstract

Phospholipase C is a key enzyme in phosphoinositide turnover. Although its functions have been extensively studied at the cellular level, many questions remain concerning its functions at the organ and individual animal levels. Here we demonstrate that mice lacking phospholipase Cδ1 develop granulocytosis associated with elevated serum levels of the granulopoietic cytokine interleukin-17. Re-introduction of phospholipase Cδ1 into keratinocytes of phospholipase Cδ1-deficient mice reverses this phenotype, whereas conditional ablation of phospholipase Cδ1 in keratinocytes recreates it. Interleukin-17 and its key upstream regulator interleukin-23 are also upregulated in epidermis. Loss of phospholipase Cδ1 from keratinocytes causes features of interleukin-17-associated inflammatory skin diseases. Phospholipase Cδ1 protein is downregulated in the epidermis of human psoriatic skin and in a mouse model of psoriasis. These results demonstrate that phosphoinositide turnover in keratinocytes regulates not only local inflammatory responses but also serum cytokine levels and systemic leukocyte counts, and affects distant haematopoietic organs.

Suggested Citation

  • Kaori Kanemaru & Yoshikazu Nakamura & Kojiro Sato & Ryota Kojima & Saori Takahashi & Mami Yamaguchi & Manabu Ichinohe & Hiroshi Kiyonari & Go Shioi & Kenji Kabashima & Kyoko Nakahigashi & Masataka Asa, 2012. "Epidermal phospholipase Cδ1 regulates granulocyte counts and systemic interleukin-17 levels in mice," Nature Communications, Nature, vol. 3(1), pages 1-12, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1960
    DOI: 10.1038/ncomms1960
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    Cited by:

    1. Kaori Kanemaru & Makoto Shimozawa & Manabu Kitamata & Rikuto Furuishi & Hinako Kayano & Yui Sukawa & Yuuki Chiba & Takatsugu Fukuyama & Junya Hasegawa & Hiroki Nakanishi & Takuma Kishimoto & Kazuya Ts, 2022. "Plasma membrane phosphatidylinositol (4,5)-bisphosphate is critical for determination of epithelial characteristics," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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