@article{8173237c1b0b4f69a93ef1864fb34cf4,
title = "Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation",
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.",
author = "Hiroki Kabata and Kazuyo Moro and Koichi Fukunaga and Yusuke Suzuki and Jun Miyata and Katsunori Masaki and Tomoko Betsuyaku and Shigeo Koyasu and Koichiro Asano",
note = "Funding Information: We thank S. Nakae and H. Watarai for materials; K. Hidaka and T. Higashide for animal care; S. Kagawa and M. Yamamoto for help with some experiments; and N. Takeno and M. Mochizuki for sorting NH cells. This work was supported in part by PRESTO to K.M. from the Japan Science and Technology Agency, a Grant-in-Aid for Young Scientist (A) (22689013) to K.M., a Grant-in-Aid for Scientific Research (S) (22229004) to S.K. and a Grant-in-Aid for Scientific Research (C) (21590971) to K.A. from the Japan Society for the Promotion of Science (JSPS), a Grant-in-Aid for Scientific Research on Innovative Areas (23118526) to K.M. from the Ministry of Education, Culture, Sports, Science and Technology, Japan, Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research to T.B. from Keio University, and a Grant-in-Aid for the Research on allergic disease and Immunology to K.A. from the Ministry of Health, Labour and Welfare, Japan.",
year = "2013",
month = oct,
day = "25",
doi = "10.1038/ncomms3675",
language = "English",
volume = "4",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}