Institute of Physiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Institute of Physiology, Berlin Institute of Health, Berlin, Germany.
Front Immunol. 2020 Mar 10;11:413. doi: 10.3389/fimmu.2020.00413. eCollection 2020.
Transient receptor potential vanilloid-type 4 (TRPV4) cation channel is widely expressed in all tissues as well as in immune cells and its function as mechanosensitive Ca channel seems to be conserved throughout all mammalian species. Of late, emerging evidence has implicated TRPV4 in the activation and differentiation of innate immune cells, especially in neutrophils, monocytes, and macrophages. As such, TRPV4 has been shown to mediate neutrophil adhesion and chemotaxis, as well as production of reactive oxygen species in response to pro-inflammatory stimuli. In macrophages, TRPV4 mediates formation of both reactive oxygen and nitrogen species, and regulates phagocytosis, thus facilitating bacterial clearance and resolution of infection. Importantly, TRPV4 may present a missing link between mechanical forces and immune responses. This connection has been exemplary highlighted by the demonstrated role of TRPV4 in macrophage activation and subsequent induction of lung injury following mechanical overventilation. Mechanosensation via TRPV4 is also expected to activate innate immune cells and establish a pro-inflammatory loop in fibrotic diseases with increased deposition of extracellular matrix (ECM) and substrate stiffness. Likewise, TRPV4 may be activated by cell migration through the endothelium or the extracellular matrix, or even by circulating immune cells squeezing through the narrow passages of the pulmonary or systemic capillary bed, a process that has recently been linked to neutrophil priming and depriming. Here, we provide an overview over the emerging role of TRPV4 in innate immune responses and highlight two distinct modes for the activation of TRPV4 by either mechanical forces ("mechanoTRPV4") or by pathogens ("immunoTRPV4").
瞬时受体电位香草酸型 4 (TRPV4) 阳离子通道广泛表达于所有组织以及免疫细胞中，其作为机械敏感 Ca2+通道的功能在所有哺乳动物物种中似乎都是保守的。最近的研究证据表明，TRPV4 参与了固有免疫细胞的激活和分化，特别是中性粒细胞、单核细胞和巨噬细胞。因此，TRPV4 已被证明介导中性粒细胞的黏附和趋化作用，以及对促炎刺激物产生活性氧物质。在巨噬细胞中，TRPV4 介导活性氧和氮物质的形成，并调节吞噬作用，从而促进细菌清除和感染的解决。重要的是，TRPV4 可能在机械力和免疫反应之间提供了一个缺失的环节。TRPV4 在机械过度通气后巨噬细胞的激活和随后诱导的肺损伤中的作用已经证明了这一联系。通过 TRPV4 的机械感觉预计也会激活固有免疫细胞，并在细胞外基质 (ECM) 沉积增加和基质硬度增加的纤维化疾病中建立促炎循环。同样，TRPV4 可能通过细胞穿过内皮细胞或细胞外基质的迁移而被激活，甚至通过循环免疫细胞通过肺或全身毛细血管床的狭窄通道挤压而被激活，最近这一过程与中性粒细胞的启动和去启动有关。在这里，我们概述了 TRPV4 在固有免疫反应中的新作用，并强调了 TRPV4 由机械力（“机械 TRPV4”）或病原体（“免疫 TRPV4”）激活的两种不同模式。
