Serotonin is primarily known for its roles in the CNS, but it is also produced by Tph2-expressing enteric neurons. A study published in Nature Communications by Zhang et al. suggests that enteric serotonergic neurons influence gut immune function. The authors observed that mice with constitutive or enteric neuron-specific loss of Tph2 have increased susceptibility to oral infection from the bacterial pathogen Salmonella and decreased activation of CD45+ immune cells within the lamina propria region of the small intestine. They pinpointed HTR7 as the main serotonin receptor expressed in these cells and found that wild-type mice treated with an HTR7 antagonist were also susceptible to oral Salmonella infection. HTR7 inhibition limited the migration of dendritic cells to the lamina propria. Enteric neurons were positioned in close proximity to dendritic cells in the lamina propria, and CellChat analysis of single-cell RNA sequencing data predicted interactions between immune-related ligands from enteric neurons and receptors on dendritic cells that could promote dendritic cell function. Although future work is required to confirm a direct synaptic interaction between these cells, this study suggests that enteric serotonergic neurons are involved in regulating the localization and function of gut immune cells.

Original reference: Nat. Commun. 15, 9237 (2024)