TRPA1 Expression and Pathophysiology in Immune Cells
The non-selective cation channel TRPA1 is best known as a broadly-tuned sensor expressed in nociceptive neurons, where it plays key functions in chemo-, thermo-, and mechano-sensing. However, in this review we illustrate how this channel is expressed also in cells of the immune system. TRPA1 has been detected, mainly with biochemical techniques, in eosinophils, mast cells, macrophages, dendritic cells, T cells, and B cells, but not in neutrophils. Functional measurements, in contrast, remain very scarce. No studies have been reported in basophils and NK cells. TRPA1 in immune cells has been linked to arthritis (neutrophils), anaphylaxis and atopic dermatitis (mast cells), atherosclerosis, renal injury, cardiac hypertrophy and inflammatory bowel disease (macrophages), and colitis (T cells). The contribution of TRPA1 to immunity is dual: as detector of cell stress, tissue injury, and exogenous noxious stimuli it leads to defensive responses, but in conditions of aberrant regulation it contributes to the exacerbation of inflammatory conditions. Future studies should aim at characterizing the functional properties of TRPA1 in immune cells, an essential step in understanding its roles in inflammation and its potential as therapeutic target.
非选择性阳离子通道 TRPA1 最为人所知的是在伤害感受神经元中表达的广泛调谐的传感器，它在化学、热和机械传感中发挥关键作用。然而，在这篇综述中，我们说明了这个通道是如何在免疫系统细胞中表达的。已在嗜酸性粒细胞、肥大细胞、巨噬细胞、树突细胞、T 细胞和 B 细胞中检测到 TRPA1，主要是通过生化技术，但未在中性粒细胞中检测到。相比之下，功能测量仍然非常稀缺。没有关于嗜碱性粒细胞和 NK 细胞的研究报告。免疫细胞中的 TRPA1 与关节炎（中性粒细胞）、过敏反应和特应性皮炎（肥大细胞）、动脉粥样硬化、肾损伤、心脏肥大和炎症性肠病（巨噬细胞）以及结肠炎（T 细胞）有关。TRPA1 对免疫的贡献是双重的：作为细胞应激、组织损伤和外源性有害刺激的检测器，它会导致防御反应，但在异常调节的情况下，它会导致炎症恶化。未来的研究应旨在表征免疫细胞中 TRPA1 的功能特性，这是了解其在炎症中的作用及其作为治疗靶点的潜力的重要一步。
The immune system is a highly adaptable and versatile system capable of recognizing a wide range of pathogens, ranging from the smallest virus to the largest tapeworm.It consists of two interconnected branches: the innate and the adaptive immune system.The innate immune system is the first line of defense and is responsible for the fast, nonspecific, initial immune response. In addition to the defense mechanisms relying on barrier and clearance functions, which are mainly based on the activities of epithelial cells,the innate immunity is based on multiple cell types, including eosinophils, neutrophils,mast cells, innate lymphoid cells, macrophages, natural killer (NK) cells, and basophils(Figure 1). Sometimes, the innate immune system is capable of eliminating the pathogenby itself, but in other cases the adaptive immune system steps in. Dendritic cells link the two systems by detecting antigens and presenting them to T cells. The adaptive immune system, based on T and B cells, has a slower activation mechanism (5–6 days), but has a more targeted approach, tailored by the identity of the intruder. The proper activation and propagation of an immune reaction requires a balance between pro- and anti-inflam matory mediators. Disruption of this balance leads to the survival of the pathogen and/or the destruction of collateral healthy tissue.