Protein Tyrosine Phosphatase Non-receptor Type 22 Modulates Colitis in a Microbiota-dependent Manner

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2019 May 21

PMID 31107248

Citations 11

Authors

Marianne R Spalinger

Thomas Sb Schmidt

Marlene Schwarzfischer

Larissa Hering

Kirstin Atrott

Silvia Lang

Claudia Gottier

Annelies Geirnaert

Christophe Lacroix

Xuezhi Dai

David J Rawlings

Andrew C Chan

Christian von Mering

Gerhard Rogler

Michael Scharl

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Role of Protein Tyrosine Phosphatases in Inflammatory Bowel Disease, Celiac Disease and Diabetes: Focus on the Intestinal Mucosa.

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Regulation of T Cell Signaling and Immune Responses by PTPN22.

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Research advancements and perspectives of inflammatory bowel disease: A comprehensive review.

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Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis.

Carone M, Spalinger M, Gaultney R, Mezzenga R, Hlavackova K, Mookhoek A Nat Commun. 2023; 14(1):3489.

PMID: 37311749 PMC: 10264425. DOI: 10.1038/s41467-023-39013-3.

Intestinal Epithelial AMPK Deficiency Causes Delayed Colonic Epithelial Repair in DSS-Induced Colitis.

Olivier S, Diounou H, Pochard C, Frechin L, Durieu E, Foretz M Cells. 2022; 11(4).

PMID: 35203241 PMC: 8869996. DOI: 10.3390/cells11040590.

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