Department of Pharmacology and Physiology, Université de Montréal.
Department of Pharmacology and Physiology, Université de Montréal;
J Vis Exp. 2022 Jun 30(184). doi: 10.3791/63800.
Somatosensory neurons have evolved to detect noxious stimuli and activate defensive reflexes. By sharing means of communication, nociceptor neurons also tune host defenses by controlling the activity of the immune system. The communication between these systems is mostly adaptive, helping to protect homeostasis, it can also lead to, or promote, the onset of chronic diseases. Both systems co-evolved to allow for such local interaction, as found in primary and secondary lymphoid tissues and mucosa. Recent studies have demonstrated that nociceptors directly detect and respond to foreign antigens, immune cell-derived cytokines, and microbes. Nociceptor activation not only results in pain hypersensitivity and itching, but lowers the nociceptor firing threshold, leading to the local release of neuropeptides. The peptides that are produced by, and released from, the peripheral terminals of nociceptors can block the chemotaxis and polarization of lymphocytes, controlling the localization, duration, and type of inflammation. Recent evidence shows that sensory neurons interact with innate immune cells via cell-cell contact, for example, engaging group 2D (NKG2D) receptors on natural killer (NK) cells. Given that NK cells express the cognate receptors for various nociceptor-produced mediators, it is conceivable that nociceptors use neuropeptides to control the activity of NK cells. Here, we devise a co-culture method to study nociceptor neuron-NK cell interactions in a dish. Using this approach, we found that lumbar nociceptor neurons decrease NK cell cytokine expression. Overall, such a reductionist method could be useful to study how tumor-innervating neurons control the anticancer function of NK cells and how NK cells control the elimination of injured neurons.
伤害感受神经元进化为检测有害刺激并激活防御反射。通过共享通讯手段，伤害感受器神经元还通过控制免疫系统的活性来调节宿主防御。这些系统之间的通讯主要是适应性的，有助于保护体内平衡，但也可能导致或促进慢性疾病的发生。这两个系统共同进化，以允许在初级和次级淋巴组织和黏膜等部位进行局部相互作用。最近的研究表明，伤害感受器可以直接检测和响应外来抗原、免疫细胞衍生的细胞因子和微生物。伤害感受器的激活不仅导致疼痛过敏和瘙痒，还降低了伤害感受器的放电阈值，导致神经肽的局部释放。伤害感受器外周末端产生和释放的肽可以阻断淋巴细胞的趋化和极化，控制炎症的定位、持续时间和类型。最近的证据表明，感觉神经元通过细胞间接触与先天免疫细胞相互作用，例如，通过自然杀伤 (NK) 细胞上的 2D 组 (NKG2D) 受体来参与。鉴于 NK 细胞表达各种伤害感受器产生的介质的相应受体，可以想象伤害感受器使用神经肽来控制 NK 细胞的活性。在这里，我们设计了一种共培养方法来在培养皿中研究伤害感受器神经元-NK 细胞相互作用。使用这种方法，我们发现腰伤害感受器神经元降低了 NK 细胞细胞因子的表达。总的来说，这种简化方法可能有助于研究肿瘤支配神经元如何控制 NK 细胞的抗癌功能，以及 NK 细胞如何控制受损神经元的清除。
