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

Hiroki Kabata, Kazuyo Moro, Koichi Fukunaga, Yusuke Suzuki, Jun Miyata, Katsunori Masaki, Tomoko Betsuyaku, Shigeo Koyasu, Koichiro Asano

研究成果: Article査読

188 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号2675
ジャーナルNature communications
4
DOI
出版ステータスPublished - 2013 10 25

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

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