期刊
NATURE COMMUNICATIONS
卷 4, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms3675
关键词
-
资金
- PRESTO from the Japan Science and Technology Agency
- Japan Society for the Promotion of Science (JSPS) [22689013, 22229004, 21590971]
- Ministry of Education, Culture, Sports, Science and Technology, Japan [23118526]
- Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research from Keio University
- Ministry of Health, Labour and Welfare, Japan
- Grants-in-Aid for Scientific Research [22689013, 24659373, 25670235, 25461504, 21590971] Funding Source: KAKEN
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据