Reactive oxygen species stimulate Paneth cell plasticity and diminish antimicrobial function

ABSTRACT: The gut epithelium faces constant environmental oxidative stresses. How it responds to pathological reactive oxygen species (ROS) is not fully understood. Using Paneth cell (PC) lineage reporters and genetic tracing, we show that as PC progenitors mature, a decline in their oxidative phosphorylation (OXPHOS) activity coincides with an increased capacity to produce antimicrobial peptides (AMPs). Direct stimulation by elevated extracellular ROS, often found during gut infection and inflammation, can drive a subset of PCs into mitotic cell division. Increasing mitochondrial superoxide production via impairment or uncoupling of the respiratory electron transport chain similarly stimulated PC cell-cycle entry and dedifferentiation into various intestinal epithelial cell types. Using gain- and l

SUBMITTER: Nan Gao 

PROVIDER: S-SCDT-10_1038-S44318-026-00869-Y | biostudies-other |

REPOSITORIES: biostudies-other