@article{b0e4cd5e146b4abfa508cde9fa6ce207,
title = "DUSP10 constrains innate IL-33-mediated cytokine production in ST2hi memory-type pathogenic Th2 cells",
abstract = "ST2hi memory-type Th2 cells are identified as a pathogenic subpopulation in eosinophilic airway inflammation. These ST2hi pathogenic Th2 cells produce large amount of IL-5 upon T cell receptor stimulation, but not in response to IL-33 treatment. By contrast, IL-33 alone induces cytokine production in ST2+ group 2 innate lymphoid cells (ILC2). Here we show that a MAPK phosphatase Dusp10 is a key negative regulator of IL-33-induced cytokine production in Th2 cells. In this regard, Dusp10 is expressed by ST2hi pathogenic Th2 cells but not by ILC2, and Dusp10 expression inhibits IL-33-induced cytokine production. Mechanistically, this inhibition is mediated by DUSP10-mediated dephosphorylation and inactivation of p38 MAPK, resulting in reduced GATA3 activity. The deletion of Dusp10 renders ST2hi Th2 cells capable of producing IL-5 by IL-33 stimulation. Our data thus suggest that DUSP10 restricts IL-33-induced cytokine production in ST2hi pathogenic Th2 cells by controlling p38-GATA3 activity.",
author = "Takeshi Yamamoto and Yusuke Endo and Atsushi Onodera and Kiyoshi Hirahara and Asou, {Hikari K.} and Takahiro Nakajima and Toshio Kanno and Yasuo Ouchi and Satoshi Uematsu and Hiroshi Nishimasu and Osamu Nureki and Tumes, {Damon J.} and Naoki Shimojo and Toshinori Nakayama",
note = "Funding Information: We thank Kaoru Sugaya, Miki Kato, and Toshihiro Ito for their excellent technical assistance. This work was supported by Japan Science and Technology Agency (JST), CREST, and by grants from the Ministry of Education, Culture, Sports, Science and Technology (MEXT Japan) (Grants-in-Aid: for Scientific Research [S] #26221305, [B] #21390147, and [C] #15K06838, #17K08876, #18K07257, Young Scientists [A] #16H06224, and [B] #24790461, Challenging Exploratory Research #23659240, Scientific Research on Innovative Areas (Research in a proposed research area) 18H04665, AMED-CREST, AMED (no. JP16gm0410009); Practical Research Project for Allergic Diseases and Immunology (Research on Allergic Diseases and Immunology) fron AMED (no. JP18ek0410030). The Astellas Foundation for Research on Metabolic Disorders, The Uehara Memorial Foundation, Osaka Foundation for Promotion of Fundamental Medical Research, Kanae Foundation for the Promotion of Medical Science, Ono Medical Research Foundation, and Takeda Science Foundation. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-06468-8",
language = "English",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}