Nature: Nod2 gene defect inhibits effective recovery of intestinal fibrosis and inflammation, leading to Crohn's disease

Mutations in the NOD2 gene are risk factors for Crohn's disease.

Crohn's disease is a chronic inflammatory bowel disease that affects many people.

Crohn's disease can affect any part of the intestine.

The genetic variation of the NOD2 gene, called polymorphism, is the strongest genetic risk associated with Crohn’s disease; about 20% of the disease risk is related to the three single nucleotide polymorphisms of the gene.

However, linking the NOD2 gene to disease susceptibility is a paradox.

Prior to this study, the role of NOD2 mutations in the development of ileal fibrosis was unclear.

First, the authors used single-cell sequencing of RNA extracted from ileal inflammation tissue removed during surgery in patients with Crohn's disease.

Gene editing tools, such as CRISPR, help to quickly modify genes of interest in zebrafish.

In order to understand the function of NOD2 in differentiable human cells in vitro, the authors used peripheral blood mononuclear cells from healthy volunteers and determined whether these cells have one, two, or no mutant copies of NOD2 associated with Crohn’s disease susceptibility .

There are many interesting ways to investigate.

Bazedoxifene was originally considered to be a selective inhibitor of estrogen receptors, which raised concerns that if the drug is used to treat Crohn’s disease, it may have adverse effects on other signaling pathways.

Not everyone with Crohn's disease has a NOD2 mutation associated with disease risk.

Original source

Nayar, S.
et al.
A myeloid–stromal niche and gp130 rescue in NOD2-driven Crohn's disease, Nature https://doi.
org/10.
1038/s41586-021-03484-5 (2021).