Protein tyrosine phosphatase non-receptor type 22 modulates colitis in a microbiota-dependent manner.
- Spalinger MR Department of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
- Schmidt TS Institute of Molecular Life Science and Swiss Institute of Bioinformatics, University of Zurich, Zurich, Switzerland.
- Schwarzfischer M Department of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
- Hering L Department of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
- Atrott K Department of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
- Lang S Department of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
- Gottier C Department of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
- Geirnaert A Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
- Lacroix C Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
- Dai X Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA.
- Rawlings DJ Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA.
- Chan AC Research, Genentech Inc., South San Francisco, California, USA.
- von Mering C Institute of Molecular Life Science and Swiss Institute of Bioinformatics, University of Zurich, Zurich, Switzerland.
- Rogler G Department of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
- Scharl M Department of Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
- 2019-05-21
Published in:
- The Journal of clinical investigation. - 2019
Gastroenterology
Inflammatory bowel disease
Amino Acid Substitution
Animals
Colitis
Dextran Sulfate
Dysbiosis
Gastrointestinal Microbiome
Mice
Mice, Knockout
Mutation, Missense
Protein Tyrosine Phosphatase, Non-Receptor Type 22
English
The gut microbiota is crucial for our health, and well-balanced interactions between the host's immune system and the microbiota are essential to prevent chronic intestinal inflammation, as observed in inflammatory bowel diseases (IBD). A variant in protein tyrosine phosphatase non-receptor type 22 (PTPN22) is associated with reduced risk of developing IBD, but promotes the onset of autoimmune disorders. While the role of PTPN22 in modulating molecular pathways involved in IBD pathogenesis is well studied, its impact on shaping the intestinal microbiota has not been addressed in depth. Here, we demonstrate that mice carrying the PTPN22 variant (619W mice) were protected from acute dextran sulfate sodium (DSS) colitis, but suffered from pronounced inflammation upon chronic DSS treatment. The basal microbiota composition was distinct between genotypes, and DSS-induced dysbiosis was milder in 619W mice than in WT littermates. Transfer of microbiota from 619W mice after the first DSS cycle into treatment-naive 619W mice promoted colitis, indicating that changes in microbial composition enhanced chronic colitis in those animals. This indicates that presence of the PTPN22 variant affects intestinal inflammation by modulating the host's response to the intestinal microbiota.
- Language
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- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1172/JCI123263
- PMID 31107248
- Persistent URL
- https://sonar.ch/global/documents/264615
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