[HTML][HTML] Loss of T-cell protein tyrosine phosphatase in the intestinal epithelium promotes local inflammation by increasing colonic stem cell proliferation

S Bussières-Marmen, V Vinette… - Cellular & Molecular …, 2018 - nature.com
S Bussières-Marmen, V Vinette, J Gungabeesoon, I Aubry, LA Pérez-Quintero, ML Tremblay
Cellular & Molecular Immunology, 2018nature.com
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 …
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.
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