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| 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
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| 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.
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| 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.
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| 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 |
| E-mail(s) |
yananzhang1031@hotmail.com
|
| Phone |
86-18817575525
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| Organization name |
Soochow University
|
| Department |
Institutes of Biology and Medical Sciences
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| Lab |
Institutes of Biology and Medical Sciences
|
| Street address |
199 Renai Road
|
| City |
Suzhou |
| State/province |
Jiangsu |
| ZIP/Postal code |
215123 |
| Country |
China |
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| Platforms (1) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE124079 |
STAT4 activation by leukemia inhibitory factor confers a therapeutic effect on intestinal inflammation |
|
| Relations |
| BioProject |
PRJNA510667 |
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