美国哈佛医学院Caroline L. Sokol研究小组发现，γδ T细胞–IL-3轴通过感觉神经元调控过敏反应。相关论文于2024年9月4日在线发表在《自然》杂志上。

研究人员描述了一个γδ T细胞–IL-3信号轴，控制皮肤感觉神经元对过敏原的响应能力。研究人员定义了一种较少被研究的表皮γδ T细胞亚群，称为GD3细胞，其分泌特征性细胞因子IL-3，促进过敏性瘙痒和过敏性免疫反应的启动。

在机制上，IL-3通过JAK2依赖的方式作用于表达Il3ra的感觉神经元，降低其对过敏原激活的阈值，而不会单独引发瘙痒。此外，该γδ T细胞–IL-3信号轴通过STAT5促进神经肽的生成并启动过敏免疫反应。这些结果揭示了一个内源性的免疫调节器，位于感觉神经元对初次过敏原暴露反应的上游，调控其反应能力。该通路可能解释了个体过敏易感性的差异，并为治疗过敏性疾病开辟了新的治疗途径。

据介绍，在初次接触过敏原的个体中，感觉神经元能够直接检测并响应过敏原，导致瘙痒感和局部先天免疫细胞的激活，从而启动过敏性免疫反应。在慢性过敏性炎症的背景下，免疫因子使感觉神经元敏感化，引发病理性瘙痒。虽然这种双向的神经免疫回路推动了对过敏原的反应，但免疫细胞是否在初次接触过敏原的情况下调节神经元激活的基准点仍未知。

附：英文原文

Title: A γδ T cell–IL-3 axis controls allergic responses through sensory neurons

Author: Flayer, Cameron H., Kernin, Isabela J., Matatia, Peri R., Zeng, Xiangsunze, Yarmolinsky, David A., Han, Cai, Naik, Parth R., Buttaci, Dean R., Aderhold, Pamela A., Camire, Ryan B., Zhu, Xueping, Tirard, Alice J., McGuire, John T., Smith, Neal P., McKimmie, Clive S., McAlpine, Cameron S., Swirski, Filip K., Woolf, Clifford J., Villani, Alexandra-Chloe, Sokol, Caroline L.

Issue&Volume: 2024-09-04

Abstract: In naive individuals, sensory neurons directly detect and respond to allergens, leading to both the sensation of itch and the activation of local innate immune cells, which initiate the allergic immune response1,2. In the setting of chronic allergic inflammation, immune factors prime sensory neurons, causing pathologic itch3,4,5,6,7. Although these bidirectional neuroimmune circuits drive responses to allergens, whether immune cells regulate the set-point for neuronal activation by allergens in the naive state is unknown. Here we describe a γδ T cell–IL-3 signalling axis that controls the allergen responsiveness of cutaneous sensory neurons. We define a poorly characterized epidermal γδ T cell subset8, termed GD3 cells, that produces its hallmark cytokine IL-3 to promote allergic itch and the initiation of the allergic immune response. Mechanistically, IL-3 acts on Il3ra-expressing sensory neurons in a JAK2-dependent manner to lower their threshold for allergen activation without independently eliciting itch. This γδ T cell–IL-3 signalling axis further acts by means of STAT5 to promote neuropeptide production and the initiation of allergic immunity. These results reveal an endogenous immune rheostat that sits upstream of and governs sensory neuronal responses to allergens on first exposure. This pathway may explain individual differences in allergic susceptibility and opens new therapeutic avenues for treating allergic diseases.

DOI: 10.1038/s41586-024-07869-0

Source: https://www.nature.com/articles/s41586-024-07869-0