Activation of interferon signaling and ferroptosis in neurons during intestinal inflammation

It is predicted that gut-innervating neurons might be directly affected by intestinal inflammation but technical difficulties in purifying neurons of GI track during inflammation hampered the progress. 

The researchers perform transcriptional profiling of gut-innervating neurons during intestinal inflammation characterized by a different cytokine milieu.

The data reveal a conserved neuronal response to inflammation, including activation of the interferon and ferroptosis pathways.

Mechanistically, the authors show that the interferon signaling pathway is triggered in neurons upon inflammation and changes in lipid and arachidonic acid metabolism fuel lipid peroxidation and ferroptosis.

Deletion of the interferon receptor 1 in neurons regulated ferroptosis, neuronal loss, and consequently gut-transit time.

https://www.cell.com/neuron/fulltext/S0896-6273(25)00136-9

https://sciencemission.com/A-transcriptional-atlas-of-gut-innervating-neurons