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DOK3 maintains intestinal homeostasis by suppressing JAK2/STAT3 signaling and S100a8/9 production in neutrophils
- Source :
- Cell Death and Disease, Vol 12, Iss 11, Pp 1-10 (2021), Cell Death & Disease
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group, 2021.
-
Abstract
- How pathogenesis of inflammatory bowel disease (IBD) depends on the complex interplay of host genetics, microbiome and the immune system is not fully understood. Here, we showed that Downstream of Kinase 3 (DOK3), an adapter protein involved in immune signaling, confers protection of mice from dextran sodium sulfate (DSS)-induced colitis. DOK3-deficiency promotes gut microbial dysbiosis and enhanced colitis susceptibility, which can be reversed by the transfer of normal microbiota from wild-type mice. Mechanistically, DOK3 exerts its protective effect by suppressing JAK2/STAT3 signaling in colonic neutrophils to limit their S100a8/9 production, thereby maintaining gut microbial ecology and colon homeostasis. Hence, our findings reveal that the immune system and microbiome function in a feed-forward manner, whereby DOK3 maintains colonic neutrophils in a quiescent state to establish a gut microbiome essential for intestinal homeostasis and protection from IBD.
- Subjects :
- STAT3 Transcription Factor
Cancer Research
Neutrophils
Immunology
Biology
digestive system
Inflammatory bowel disease
Article
S100A8
Pathogenesis
Mice
Cellular and Molecular Neuroscience
Immune system
medicine
Animals
Calgranulin B
Homeostasis
Calgranulin A
Microbiome
Intestinal Mucosa
Colitis
Adaptor Proteins, Signal Transducing
QH573-671
Kinase
Microbiota
Cell Biology
Janus Kinase 2
medicine.disease
digestive system diseases
Cell biology
Intestines
Disease Models, Animal
Gene Expression Regulation
Mucosal immunology
Dysbiosis
Disease Susceptibility
Cytology
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20414889
- Volume :
- 12
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Cell Death and Disease
- Accession number :
- edsair.doi.dedup.....4e1fa458aeea2ab1aae51dc6b478a217