New research has mapped neuroimmune interactions in the mouse gut, revealing that TRPV1-expressing nociceptor neurons (involved in visceral pain) control and suppress regulatory T (T_reg) cells in the gut, increasing susceptibility to colitis in mouse models. The findings potentially link pain signalling with immunomodulatory mechanisms in the gut.

In their screen, eight distinct neuronal subsets were activated in mice and mapped. Distinct immune perturbations were observed following this activation: nitrergic neurons (NOS1 expression) regulated T helper 17-like cells in the ileum; cholinergic neurons (express choline acetyltransferase) regulated ileal neutrophils; and nociceptor neurons (TRPV1 expression) regulated a range of cell types including type 2 innate lymphoid cells, activated CD8⁺ T cells, macrophages and RORγ T_reg cells. Examining the nociceptor neurons in more detail revealed that TRPV1⁺ neurons in the dorsal root ganglia suppressed RORγ⁺ T_reg cells in the colon via calcitonin gene-related peptide, which was mediated via the receptor RAMP1–CALCRL. Importantly, TRPV1⁺ neuron activation and subsequent downregulation of T_reg cells resulted in increased susceptibility to intestinal inflammation in mice (via Citrobacter infection and induction by administration of dextran sodium sulfate).

新研究绘制了小鼠肠道中的神经免疫相互作用图谱，揭示了表达 TRPV1 的伤害感受器神经元（参与内脏疼痛）控制和抑制肠道中的调节性 T (T _reg ) 细胞，从而增加了小鼠模型对结肠炎的易感性。这些发现可能将疼痛信号传导与肠道免疫调节机制联系起来。

在他们的屏幕中，小鼠体内八个不同的神经元亚群被激活并绘制出来。这种激活后观察到了明显的免疫扰动：硝能神经元（NOS1 表达）调节回肠中的 T 辅助细胞 17 样细胞；胆碱能神经元（表达胆碱乙酰转移酶）调节回肠中性粒细胞；伤害感受器神经元（TRPV1 表达）调节一系列细胞类型，包括 2 型先天淋巴细胞、活化的 CD8 ⁺ T 细胞、巨噬细胞和 RORγ T _reg细胞。更详细地检查伤害感受器神经元发现，背根神经节中的 TRPV1 ⁺神经元通过降钙素基因相关肽抑制结肠中的 RORγ ⁺ T _reg细胞，而降钙素基因相关肽是通过受体 RAMP1-CALCRL 介导的。重要的是，TRPV1 ⁺神经元激活和随后的 T _reg细胞下调导致小鼠对肠道炎症的易感性增加（通过柠檬酸杆菌感染和给予葡聚糖硫酸钠诱导）。