Department of Pathology, Duke University Medical Center, Durham, NC.
Department of Pathology, Duke University Medical Center, Durham, NC; Department of Immunology, Duke University Medical Center, Durham, NC; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC; Department of Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore, Singapore.
J Allergy Clin Immunol. 2024 Apr;153(4):939-953. doi: 10.1016/j.jaci.2024.02.005. Epub 2024 Feb 17.
Mast cells (MCs) are tissue-resident immune cells, well-positioned at the host-environment interface for detecting external antigens and playing a critical role in mobilizing innate and adaptive immune responses. Sensory neurons are afferent neurons innervating most areas of the body but especially in the periphery, where they sense external and internal signals and relay information to the brain. The significance of MC-sensory neuron communication is now increasingly becoming recognized, especially because both cell types are in close physical proximity at the host-environment interface and around major organs of the body and produce specific mediators that can activate each other. In this review, we explore the roles of MC-sensory neuron crosstalk in allergic diseases, shedding light on how activated MCs trigger sensory neurons to initiate signaling in pruritus, shock, and potentially abdominal pain in allergy, and how activated sensory neurons regulate MCs in homeostasis and atopic dermatitis associated with contact hypersensitivity and type 2 inflammation. Throughout the review, we also discuss how these 2 sentinel cell types signal each other, potentially resulting in a positive feedback loop that can sustain inflammation. Unraveling the mysteries of MC-sensory neuron crosstalk is likely to unveil their critical roles in various disease conditions and enable the development of new therapeutic approaches to combat these maladies.
肥大细胞(MCs)是组织驻留的免疫细胞,位于宿主-环境界面,可检测外部抗原,并在调动先天和适应性免疫反应方面发挥关键作用。感觉神经元是支配身体大部分区域的传入神经元,但尤其在周围神经系统中,它们可以感知外部和内部信号,并将信息传递到大脑。现在,MC-感觉神经元通讯的重要性越来越受到重视,特别是因为这两种细胞类型在宿主-环境界面和身体主要器官周围的位置非常接近,并且产生可以相互激活的特定介质。在这篇综述中,我们探讨了 MC-感觉神经元串扰在过敏性疾病中的作用,阐明了活化的 MC 如何触发感觉神经元启动过敏反应中的瘙痒、休克和潜在腹痛信号,以及活化的感觉神经元如何在接触性超敏反应和 2 型炎症相关的稳态和特应性皮炎中调节 MC。在整个综述中,我们还讨论了这两种哨兵细胞类型如何相互传递信号,这可能导致炎症的正反馈循环。揭示 MC-感觉神经元串扰的奥秘,可能揭示它们在各种疾病状态中的关键作用,并为对抗这些疾病开发新的治疗方法。