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Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling
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Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling
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Journal Article
Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling
2024
Overview
Serotonergic neurons in the central nervous system control behavior and mood, but knowledge of the roles of serotonergic circuits in the regulation of immune homeostasis is limited. Here, we employ mouse genetics to investigate the functions of enteric serotonergic neurons in the control of immune responses and find that these circuits regulate IgA induction and boost host defense against oral, but not systemic
Salmonella
Typhimurium infection. Enteric serotonergic neurons promote gut-homing, retention and activation of intestinal plasmacytoid dendritic cells (pDC). Mechanistically, this neuro-immune crosstalk is achieved through a serotonin-5-HT receptor 7 (HTR7) signaling axis that ultimately facilitates the pDC-mediated differentiation of IgA
+
B cells from IgD
+
precursors in the gut. Single-cell RNA-seq data further reveal novel patterns of bidirectional communication between specific subsets of enteric neurons and lamina propria DC. Our findings thus reveal a close interplay between enteric serotonergic neurons and gut immune homeostasis that enhances mucosal defense.
Roles of serotonergic neurons in immune homeostasis and host defense are largely unexplored. Here the authors show that in mice enteric serotonergic neurons regulate immune homeostasis and host defense against Salmonella infection by orchestrating gut homing and activation of plasmacytoid dendritic cell, ultimately promoting the differentiation of protective IgA
+
B cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 14/1
/ 38/1
/ 38/39
/ 64
/ 64/60
/ Animals
/ Cell Differentiation - immunology
/ Circuits
/ Dendritic Cells - immunology
/ Dendritic Cells - metabolism
/ Enteric Nervous System - immunology
/ Enteric Nervous System - metabolism
/ Genetics
/ Homing
/ Humanities and Social Sciences
/ Immunoglobulin A - immunology
/ Immunoglobulin A - metabolism
/ Intestinal Mucosa - immunology
/ Intestinal Mucosa - metabolism
/ Male
/ Mice
/ Neurons
/ Receptors, Serotonin - genetics
/ Receptors, Serotonin - metabolism
/ Salmonella Infections - immunology
/ Salmonella Infections - metabolism
/ Salmonella Infections - microbiology
/ Salmonella typhimurium - immunology
/ Salmonella typhimurium - physiology
/ Science
