[HTML][HTML] DUSP10 constrains innate IL-33-mediated cytokine production in ST2hi memory-type pathogenic Th2 cells

T Yamamoto, Y Endo, A Onodera, K Hirahara… - Nature …, 2018 - nature.com
T Yamamoto, Y Endo, A Onodera, K Hirahara, HK Asou, T Nakajima, T Kanno, Y Ouchi
Nature communications, 2018nature.com
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 …
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.
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