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Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation

Author

Listed:
  • Hiroki Kabata

    (Keio University School of Medicine
    Keio University School of Medicine
    Laboratory for Immune Cell System, RCAI, RIKEN Research Center for Integrative Medical Sciences (IMS-RCAI))

  • Kazuyo Moro

    (Laboratory for Immune Cell System, RCAI, RIKEN Research Center for Integrative Medical Sciences (IMS-RCAI)
    Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency
    Graduate School of Medical Life Science, Yokohama City University)

  • Koichi Fukunaga

    (Keio University School of Medicine)

  • Yusuke Suzuki

    (Keio University School of Medicine)

  • Jun Miyata

    (Keio University School of Medicine)

  • Katsunori Masaki

    (Keio University School of Medicine)

  • Tomoko Betsuyaku

    (Keio University School of Medicine)

  • Shigeo Koyasu

    (Keio University School of Medicine
    Laboratory for Immune Cell System, RCAI, RIKEN Research Center for Integrative Medical Sciences (IMS-RCAI))

  • Koichiro Asano

    (Keio University School of Medicine
    Tokai University School of Medicine)

Abstract

Type-2 innate immune responses that occur in airways and are accompanied by goblet-cell hyperplasia and mucus production are largely driven by interleukin-33 (IL-33) and natural helper (NH) cells, a member of group 2 innate lymphoid cells (ILC2s) and the major target of IL-33. Here we report that the corticosteroid resistance observed as a result of airway inflammation triggered by sensitization and exposure to allergen is induced via the IL-33/NH-cell axis. Thymic stromal lymphopoietin (TSLP) synthesized during airway inflammation plays a pivotal role in the induction of NH-cell corticosteroid resistance in vitro and in vivo, by controlling phosphorylation of STAT5 and expression of Bcl-xL in NH cells. Blockade of TSLP with a neutralizing antibody or blocking the TSLP/STAT5 signalling pathway with low molecular-weight STAT5 inhibitors such as pimozide restores corticosteroid sensitivity. Thus, the TSLP-STAT5 pathway could be a new therapeutic target in severe, corticosteroid-resistant asthma.

Suggested Citation

  • Hiroki Kabata & Kazuyo Moro & Koichi Fukunaga & Yusuke Suzuki & Jun Miyata & Katsunori Masaki & Tomoko Betsuyaku & Shigeo Koyasu & Koichiro Asano, 2013. "Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation," Nature Communications, Nature, vol. 4(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3675
    DOI: 10.1038/ncomms3675
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    1. Yuying Huang & Lin Zhu & Shipeng Cheng & Ranran Dai & Chunrong Huang & Yanyan Song & Bo Peng & Xuezhen Li & Jing Wen & Yi Gong & Yunqian Hu & Ling Qian & Linyun Zhu & Fengying Zhang & Li Yu & Chunyan , 2023. "Solar ultraviolet B radiation promotes α-MSH secretion to attenuate the function of ILC2s via the pituitary–lung axis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Natsuko Otaki & Yasutaka Motomura & Tommy Terooatea & S. Thomas Kelly & Miho Mochizuki & Natsuki Takeno & Shigeo Koyasu & Miu Tamamitsu & Fuminori Sugihara & Junichi Kikuta & Hideya Kitamura & Yoshiki, 2023. "Activation of ILC2s through constitutive IFNγ signaling reduction leads to spontaneous pulmonary fibrosis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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