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Series GSE116842 Query DataSets for GSE116842
Status Public on Sep 23, 2018
Title DUSP10 constrains innate IL-33-mediated cytokine production in ST2hi memory-type pathogenic Th2 cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Memory CD4+ T helper (Th) cells are crucial for acquired immunity and protection from infectious microorganisms, and also drive pathogenesis of chronic inflammatory diseases, such as asthma. ST2hi memory-type Th2 cells have been identified as a pathogenic subpopulation capable of directly inducing eosinophilic airway inflammation. These ST2hi pathogenic Th2 cells produce large amounts of IL-5 upon stimulation via their TCR, but not in response to IL-33. In contrast, IL-33 alone induces cytokine production in ST2+ group 2 innate lymphoid cells (ILC2). We investigated the molecular mechanism that controls the innate function of IL-33-induced cytokine production, and identified a MAPK phosphatase Dusp10, as a key negative regulator of IL-33–induced cytokine production in Th2 cells. We found that Dusp10 is expressed by ST2hi pathogenic Th2 cells but not by ILC2, and Dusp10 expression inhibits IL-33-induced cytokine production by preventing GATA3 activity through inhibition of p38 MAPK phosphorylation. Strikingly, deletion of Dusp10 rendered ST2hi Th2 cells able to directly respond to IL-33 exposure and produce IL-5. Thus, DUSP10 constrains IL-33–induced cytokine production in ST2hi pathogenic Th2 cells by controlling p38-mediated GATA3 function.
 
Overall design Functions of Dusp10, a family of dual specificity protein phosphatase, are assessed by RNA-seq.
 
Contributor(s) Yamamoto T, Endo Y, Onodera A, Hirahara K, Asou HK, Nakajima T, Kanno T, Ouchi Y, Uematsu S, Nishimasu H, Nureki O, Tumes DJ, Shimojo N, Nakayama T
Citation(s) 30315197
Submission date Jul 10, 2018
Last update date Oct 17, 2018
Contact name Yusuke ENDO
E-mail(s) san3tamariayuyu@chiba-u.jp
Phone 81432262186
Organization name Chiba University
Department Immunology
Lab Immunology
Street address 1-8-1 Inohana, Chuo-ku
City Chiba-city
State/province Chiba
ZIP/Postal code 260-8670
Country Japan
 
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (3)
GSM3262712 Tpath2_RNA
GSM3262713 ILC2_RNA
GSM3262714 Th2_RNA
Relations
BioProject PRJNA480393
SRA SRP152919

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE116842_RAW.tar 400.0 Kb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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