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Loss of T-cell protein tyrosine phosphatase in the intestinal epithelium promotes local inflammation by increasing colonic stem cell proliferation
- Source :
- Cellular and Molecular Immunology
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- T-cell protein tyrosine phosphatase (TC-PTP) has a critical role in the development of the immune system and has been identified as a negative regulator of inflammation. Single-nucleotide polymorphisms in the TC-PTP locus have been associated with increased susceptibility to inflammatory bowel diseases (IBDs) in patients. To further understand how TC-PTP is related to IBDs, we investigated the role of TC-PTP in maintaining the intestinal epithelial barrier using an in vivo genetic approach. Intestinal epithelial cell (IEC)-specific deletion of TC-PTP was achieved in a mouse model at steady state and in the context of dextran sulphate sodium (DSS)-induced colitis. Knockout (KO) of TC-PTP in IECs did not result in an altered intestinal barrier. However, upon DSS treatment, IEC-specific TC-PTP KO mice displayed a more severe colitis phenotype with a corresponding increase in the immune response and inflammatory cytokine profile. The absence of TC-PTP caused an altered turnover of IECs, which is further explained by the role of the tyrosine phosphatase in colonic stem cell (CoSC) proliferation. Our results suggest a novel role for TC-PTP in regulating the homeostasis of CoSC proliferation. This supports the protective function of TC-PTP against IBDs, independently of its previously demonstrated role in intestinal immunity.
- Subjects :
- 0301 basic medicine
animal structures
TC-PTP
Colon
Neutrophils
Colonic stem cells
Immunology
Inflammation
Protein tyrosine phosphatase
Biology
digestive system
environment and public health
Article
03 medical and health sciences
Immune system
Intestinal mucosa
medicine
Animals
Homeostasis
Immunology and Allergy
Intestinal Mucosa
Colitis
DSS-induced colitis
Cell Proliferation
Mice, Knockout
Protein Tyrosine Phosphatase, Non-Receptor Type 2
Cell growth
Stem Cells
Dextran Sulfate
medicine.disease
Intestinal epithelium
digestive system diseases
3. Good health
Cell biology
Mice, Inbred C57BL
enzymes and coenzymes (carbohydrates)
Enterocytes
030104 developmental biology
Infectious Diseases
intestinal epithelial barrier
Cytokines
Disease Susceptibility
medicine.symptom
Stem cell
Subjects
Details
- ISSN :
- 20420226 and 16727681
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- Cellular & Molecular Immunology
- Accession number :
- edsair.doi.dedup.....31a5d17880297956ea96e32fa4895b9c