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)

血清素主要因其在 CNS 中的作用而闻名，但它也由表达 Tph2 的肠道神经元产生。Zhang 等人发表在 Nature Communications 上的一项研究表明，肠道血清素能神经元会影响肠道免疫功能。作者观察到，具有 Tph2 组成型或肠道神经元特异性缺失的小鼠对细菌病原体沙门氏菌口腔感染的易感性增加，并且小肠固有层区域内 CD45⁺ 免疫细胞的激活降低。他们确定 HTR7 是这些细胞中表达的主要 5-羟色胺受体，并发现用 HTR7 拮抗剂治疗的野生型小鼠也容易受到口服沙门氏菌感染。HTR7 抑制限制了树突状细胞向固有层的迁移。肠道神经元位于固有层中的树突状细胞附近，单细胞 RNA 测序数据的 CellChat 分析预测了来自肠道神经元的免疫相关配体与树突状细胞上的受体之间的相互作用，这些相互作用可以促进树突状细胞功能。尽管需要未来的工作来证实这些细胞之间的直接突触相互作用，但这项研究表明，肠道血清素能神经元参与调节肠道免疫细胞的定位和功能。

原始参考：Nat. Commun.15， 9237 （2024）