Respiratory Institute, Cleveland Clinic, Cleveland, OH, United States.
Department of Pulmonary and Critical Care, Virginia Commonwealth University, Richmond, VA, United States.
Front Immunol. 2021 Nov 2;12:767319. doi: 10.3389/fimmu.2021.767319. eCollection 2021.
The importance of innate immune cells to sense and respond to their physical environment is becoming increasingly recognized. Innate immune cells (e.g. macrophages and neutrophils) are able to receive mechanical signals through several mechanisms. In this review, we discuss the role of mechanosensitive ion channels, such as Piezo1 and transient receptor potential vanilloid 4 (TRPV4), and cell adhesion molecules, such as integrins, selectins, and cadherins in biology and human disease. Furthermore, we explain that these mechanical stimuli activate intracellular signaling pathways, such as MAPK (p38, JNK), YAP/TAZ, EDN1, NF-kB, and HIF-1α, to induce protein conformation changes and modulate gene expression to drive cellular function. Understanding the mechanisms by which immune cells interpret mechanosensitive information presents potential targets to treat human disease. Important areas of future study in this area include autoimmune, allergic, infectious, and malignant conditions.
先天免疫细胞感知和响应其物理环境的重要性正日益受到重视。先天免疫细胞（如巨噬细胞和中性粒细胞）能够通过几种机制接收机械信号。在这篇综述中，我们讨论了机械敏感离子通道（如 Piezo1 和瞬时受体电位香草素 4（TRPV4））以及细胞黏附分子（如整合素、选择素和钙黏蛋白）在生物学和人类疾病中的作用。此外，我们解释了这些机械刺激激活细胞内信号通路，如 MAPK（p38、JNK）、YAP/TAZ、EDN1、NF-kB 和 HIF-1α，以诱导蛋白质构象变化并调节基因表达，从而驱动细胞功能。了解免疫细胞解释机械敏感信息的机制为治疗人类疾病提供了潜在的靶点。该领域未来的重要研究领域包括自身免疫、过敏、感染和恶性疾病。
