Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling

Area of Science:

• Neuroscience
• Immunology
• Gastroenterology

Background:

• Serotonergic neurons regulate mood and behavior, but their role in immune homeostasis is not well understood.
• The gut-brain axis and neuro-immune interactions are critical for maintaining health.

Purpose of the Study:

• To investigate the function of enteric serotonergic neurons in regulating immune responses within the gut.
• To elucidate the mechanisms by which these neurons influence mucosal immunity and host defense.

Main Methods:

• Mouse genetics to study enteric serotonergic neuron function.
• Analysis of immune cell populations, including plasmacytoid dendritic cells (pDCs) and B cells.
• Single-cell RNA sequencing to identify neuro-immune communication pathways.

Main Results:

• Enteric serotonergic neurons regulate immunoglobulin A (IgA) induction and enhance defense against oral Salmonella Typhimurium infection.
• These neurons promote the gut-homing, retention, and activation of intestinal pDCs.
• A serotonin-5-HT receptor 7 (HTR7) signaling axis facilitates pDC-mediated differentiation of IgA+ B cells.

Conclusions:

• Enteric serotonergic neurons play a crucial role in maintaining gut immune homeostasis.
• Neuro-immune crosstalk via the HTR7 pathway enhances mucosal defense against enteric pathogens.
• Bidirectional communication exists between enteric neurons and dendritic cells in the gut lamina propria.