Study shows tofacitinib medication can fix porousness absconds in the digestive tract

Study shows tofacitinib medication can fix porousness absconds in the digestive tract


  • Post By : Kumar Jeetendra

  • Source: University of California-Riverside

  • Date: 06 Oct,2020

A team of researchers led by biomedical scientist Declan F. McCole in the University of California, Riverside, has found that the medication tofacitinib, also called Xeljanz and approved by the FDA to treat rheumatoid arthritis and ulcerative colitis, can fix permeability defects in the intestine.

Study results appear in the Journal of Crohn’s and Colitis.

Affecting roughly 1 million Americans, ulcerative colitis, an inflammatory bowel disease, is a chronic disease of the large intestine, in which the lining of the colon becomes inflamed and leaky.

A single layer of cells that plays a vital role in human health, the intestinal epithelium provides a barrier whilst also allowing water and nutrient absorption.

The body’s largest pool of immune cells can be found directly beneath the epithelial cell layer.

The current study is a follow-up to two recently published studies from McCole’s lab. In the first study, published in December 2019, the researchers used a cell culture model system to prove that tofacitinib can directly act on epithelial cells which line the gut to correct defects in the barrier properties of these cells which exist in inflammation.

Our work could help improve identification of patients who will be better responders to this drug.”-McCole, Professor of Biomedical Sciences, School of Medicine, University of California-Riverside

The second study, published in July 2020, revealed a loss-of-function mutation in the gene”protein tyrosine phosphatase non-receptor Type 2,” or PTPN2, interrupted normal beneficial interactions between epithelial cells and macrophages — a sort of white blood cell that constitutes a considerable fraction of intestinal immune cells — and increased gut leakiness.

In the new study, the authors reveal tofacitinib can reverse gut leakiness in mice caused by reduction of PTPN2 activity.

McCole clarified that increased intestinal permeability — or leakiness — is a characteristic of inflammatory bowel disease and plays a crucial role in promoting inflammation.

His team also analyzed tofacitinib in a method where PTPN2 expression was reduced in human intestinal epithelial cell lines and macrophages that were then cultured together to study the effects on epithelial permeability.

The group also studied mice that had increased gut leakiness resulting from removal of PTPN2 just in macrophages.

“Patients with the loss-of-function mutations in PTPN2 have an increased risk of inflammatory bowel disease,” McCole said.

“Our work improves our understanding of how this drug is useful for treating ulcerative colitis and suggests that patients with loss-of-function mutations in the PTPN2 gene might have a better response to tofacitinib. This could help with improved targeting of drug treatments to specific groups of individuals.”

Journal reference:

Spalinger, M. R., et al. (2020) The JAK inhibitor tofacitinib rescues intestinal barrier defects caused by disrupted epithelial-macrophage interactions. Journal of Crohn’s and Colitis.

About Author