University of California, Riverside-led study reveals how IBD develops

inflammatory bowel disease, or IBDdescribes Crohn’s disease and ulcerative colitis, two chronic diseases that cause inflammation in the intestines. Affecting approximately 3 million adults in the United States, IBD is an autoimmune disease, a condition in which the body’s immune system attacks healthy tissue. Its symptoms include diarrhea, rectal bleeding, fatigue, weight loss, and stomach cramps.

The intestinal epithelium, which consists of the layer of cells lining the intestine, plays an important role in IBD as it can be easily destroyed during intestinal inflammation. A special type of epithelial cell is the Paneth cell. The antimicrobial peptides produced by these cells help regulate the gut microbiome, or the microbial community that resides in the gut.

A research team led by Declan F. McCallA biomedical scientist and IBD expert at the University of California, Riverside, has shown in mouse studies that reduced activity of the IBD risk gene PTPN2 in intestinal epithelial cells may lead to reduced production of Paneth cell antimicrobial peptides. reporting.

of studyPublished in Cellular and Molecular Gastroenterology and Hepatology.

“This study is focused on improving personalized medicine approaches in IBD by understanding how patients with variants in the PTPN2 gene develop IBD. Faculty of Medicine“Loss of PTPN2 may also lead to selective loss of Paneth cells in the intestinal epithelium. Loss of this PTPN2 causes profound changes in the gut microbiota, increasing certain E. coli.”

Escherichia coli, or E. coli, is a bacterium found in the environment, food, and the intestines of humans and animals. McCole explained that the problem E. coli, adherent invasive E. coli, or AIEC increased in his IBD, exacerbating inflammation. First identified in patients with Crohn’s disease, AIEC can adhere to and invade epithelial cells as well as immune cells called macrophages.

“AIEC is a strong candidate for a causal role of bacteria in IBD,” he said.

In many IBD patients, Paneth cells do not function properly, which could serve as a marker of the disease, says McCole. The antimicrobial peptides produced by these cells are critically linked to the intestinal protective barrier for regulating the relative proportions of bacteria and interactions between them. They also help adjacent intestinal stem cells to function better.

“In IBD, Paneth cells often fail to produce enough antimicrobial peptides or respond appropriately to gut bacteria,” McCole said. may also be associated with structural changes in Paneth cells that reduce their ability to secrete , leading to increased populations of IBD-associated bacteria such as AIEC. also serves as a marker for disease in IBD, especially Crohn’s disease.”

McCole participated in research by Vinicius Canale, Marianne R. Spalinger, Rocio Alvarez, Anica Sayoc-Becerra, Golshid Sanati, Salomon Manz, Pritha Chatterjee, Alina N. Santos, Hillmin Lei, Sharon Jahng, Timothy Chu, and Ali Shawki. bottom. UCR; Elaine Hanson and Lars Eckman of the University of California, San Diego. Andre J. Ouellet of the University of Southern California.

This research was supported by the Crohn’s Disease and Colitis Foundation. Swiss National Science Foundation. American Society of Gastroenterology; Sciences Without Borders; and California Institute for Regenerative Medicine.

“This study lays the groundwork for our new research project to identify pharmacological agents that can rescue Paneth cell function and reduce the microbial contribution to intestinal inflammation,” said McCole. increase.

of research paper the title is”PTPN2 is a key regulator of murine ileal Paneth cell viability and function. ”

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