A myeloid–stromal niche and gp130 rescue in NOD2-driven Crohn’s disease

Abstract

Crohn's disease is a chronic inflammatory intestinal disease that is frequently accompanied by aberrant healing and stricturing complications. Crosstalk between activated myeloid and Reprints and permissions information is available at http://www.nature.com/reprints.

Single-cell transcriptomic profiling of healthy and fibrotic adult zebrafish liver reveals conserved cell identities and stellate cell activation phenotypes with human liver

“…A list of human-to-fish orthologs was generated using ZFIN zebrafish–human orthologs database (20 August 2020) (24). The orthologs in the database were curated considering three factors: conserved genome location, amino acid sequence comparison and the phylogenetics tree.…”

“…To develop a single-cell atlas of adult zebrafish liver, livers were dissected from 18-month-old wild-type zebrafish (WT; N = 3). Single-cell suspensions were generated following previously published protocols (24), with cell viabilities from each sample ranging from 72 to 81%. After mitochondrial RNA percentage, unique molecular identifier (UMI), and gene cutoffs were implemented, a range of 3,742 to 5,544 profiled cells (N = 13,630 cells) from each sample were used for further analysis.…”

A molecular connection hints at how a genetic risk factor drives Crohn’s disease

“…b, Mutations that generate a non-functional version of NOD2 are a risk factor for Crohn's disease 4 . Studying zebrafish and clinical samples, Nayar et al 2 reveal details of processes underlying the disease that are associated with mutant NOD2. The authors identify populations of activated immune cells called macrophages and fibroblasts as being responsible for fibrosis, a tissue abnormality in the ileum region of the bowel that occurs in Crohn's disease.…”

“…Better therapies are needed, but progress in treating Crohn's disease has been hampered by the lack of understanding of how it arises. Writing in Nature, Nayar et al 2 shed light on a long-standing mystery about one risk factor for Crohn's disease, and their findings have important clinical implications.…”

From good to bad fibroblasts: New promising targets to cure Crohn's disease

“…Although many therapeutic strategies have been beneficial to block inflammation in CD, no improvement has been made in providing therapeutic strategies to reduce fibrosis. Increasing evidence suggests that the long-lasting inflammation associated with CD is a consequence of activated fibroblasts [2]. However, the mechanisms responsible for fibroblast activation appeared to be independent of those related to immune cell activation [3,4].…”