NOX1 is essential for TNFα-induced intestinal epithelial ROS secretion and inhibits M cell signatures.

ABSTRACT:

Objective

Loss-of-function mutations in genes generating reactive oxygen species (ROS), such as NOX1, are associated with IBD. Mechanisms whereby loss of ROS drive IBD are incompletely defined.

Design

ROS measurements and single-cell transcriptomics were performed on colonoids stratified by NOX1 genotype and TNFα stimulation. Clustering of epithelial cells from human UC (inflamed and uninflamed) scRNASeq was performed. Validation of M cell induction was performed by immunohistochemistry using UEA1 (ulex europaeus agglutin-1 lectin) and in vivo with DSS injury.

Results

TNFα induces ROS production more in NOX1-WT versus NOX1-deficient murine colonoids under a range of Wnt-mediated and Notch-mediated conditions. scRNASeq from inflamed and uninflamed human c

SUBMITTER: Hsu NY 

PROVIDER: S-EPMC9998338 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature