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Series GSE124078 Query DataSets for GSE124078
Status Public on Dec 18, 2019
Title STAT4 activation by leukemia inhibitory factor confers a therapeutic effect on intestinal inflammation [array]
Organism Mus musculus
Experiment type Expression profiling by array
Summary T helper 17 (Th17) cell differentiation triggered by interleukin-6 (IL-6) via STAT3 activation promotes inflammation in inflammatory bowel disease (IBD) patients. However, leukemia inhibitory factor (LIF), an IL-6 family cytokine, restricts inflammation by blocking Th17 cell differentiation via an unknown mechanism. Here, we report that microbiota dysregulation promotes LIF secretion by intestinal epithelial cells (IECs) in a mouse colitis model. LIF greatly activates STAT4 phosphorylation on multiple SPXX elements within the C-terminal transcription regulation domain. STAT4 and STAT3 act reciprocally on both canonical cis-inducible elements (SIEs) and noncanonical “AGG” elements at different loci. In lamina propria lymphocytes (LPLs), STAT4 activation by LIF blocks STAT3-dependent Il-17a/Il-17f promoter activation, whereas in IECs, LIF bypasses the extraordinarily low level of STAT4 to induce YAP gene expression via STAT3 activation. In addition, we found that the administration of LIF is sufficient to restore microbiome homeostasis. Thus, LIF effectively inhibits Th17 accumulation and promotes repair of damaged intestinal epithelium in inflamed colon, and serves as a potential therapy for IBD.
Overall design The gene expression in lamina propria lymphocytes (LPLs) of wild-type and Stat4-knockout mice were measured on day 10 after exposure to dextran sulfate sodium (DSS) solution, or DSS solution and LIF-treatment. Five mice were used to isolate LPLs for each group.
Contributor(s) Zhang YS, Chin YE
Citation(s) 30770344
Submission date Dec 18, 2018
Last update date Mar 19, 2020
Contact name Yanan S Zhang
Phone 86-18817575525
Organization name Soochow University
Department Institutes of Biology and Medical Sciences
Lab Institutes of Biology and Medical Sciences
Street address 199 Renai Road
City Suzhou
State/province Jiangsu
ZIP/Postal code 215123
Country China
Platforms (1)
GPL11202 Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version)
Samples (4)
GSM3520239 wt_dss_LPLs
GSM3520240 wt_dss_lif_LPLs
GSM3520241 ko_dss_LPLs
This SubSeries is part of SuperSeries:
GSE124079 STAT4 activation by leukemia inhibitory factor confers a therapeutic effect on intestinal inflammation
BioProject PRJNA510667

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
GSE124078_RAW.tar 8.4 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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