| First Author | Yamamoto T | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 4231 |
| PubMed ID | 30315197 | Mgi Jnum | J:267739 |
| Mgi Id | MGI:6268261 | Doi | 10.1038/s41467-018-06468-8 |
| Citation | Yamamoto T, et al. (2018) DUSP10 constrains innate IL-33-mediated cytokine production in ST2(hi) memory-type pathogenic Th2 cells. Nat Commun 9(1):4231 |
| abstractText | ST2(hi) memory-type Th2 cells are identified as a pathogenic subpopulation in eosinophilic airway inflammation. These ST2(hi) 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 ST2(hi) 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 ST2(hi) Th2 cells capable of producing IL-5 by IL-33 stimulation. Our data thus suggest that DUSP10 restricts IL-33-induced cytokine production in ST2(hi) pathogenic Th2 cells by controlling p38-GATA3 activity. |
