Ramirez Giuseppe A, Coletto Lavinia A, Sciorati Clara, Bozzolo Enrica P, Manunta Paolo, Rovere-Querini Patrizia, Manfredi Angelo A
Unit of Immunology, Rheumatology, Allergy and Rare Diseases, Università Vita-Salute San Raffaele, 20132 Milan, Italy.
Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS Ospedale San Raffaele, 20132 Milan, Italy.
Cells. 2018 Jul 4;7(7):70. doi: 10.3390/cells7070070.
Allergy and autoimmune diseases are characterised by a multifactorial pathogenic background. Several genes involved in the control of innate and adaptive immunity have been associated with diseases and variably combine with each other as well as with environmental factors and epigenetic processes to shape the characteristics of individual manifestations. Systemic or local perturbations in salt/water balance and in ion exchanges between the intra- and extracellular spaces or among tissues play a role. In this field, usually referred to as elementary immunology, novel evidence has been recently acquired on the role of members of the transient potential receptor (TRP) channel family in several cellular mechanisms of potential significance for the pathophysiology of the immune response. TRP canonical channel 6 (TRPC6) is emerging as a functional element for the control of calcium currents in immune-committed cells and target tissues. In fact, TRPC6 influences leukocytes’ tasks such as transendothelial migration, chemotaxis, phagocytosis and cytokine release. TRPC6 also modulates the sensitivity of immune cells to apoptosis and influences tissue susceptibility to ischemia-reperfusion injury and excitotoxicity. Here, we provide a view of the interactions between ion exchanges and inflammation with a focus on the pathogenesis of immune-mediated diseases and potential future therapeutic implications.
过敏和自身免疫性疾病具有多因素致病背景。一些参与固有免疫和适应性免疫调控的基因与疾病相关，它们相互之间以及与环境因素和表观遗传过程以不同方式组合，从而形成个体临床表现的特征。盐/水平衡以及细胞内和细胞外空间之间或组织间离子交换的全身或局部紊乱也发挥作用。在这个通常被称为基础免疫学的领域，最近获得了关于瞬时电位受体（TRP）通道家族成员在免疫反应病理生理学中具有潜在重要意义的几种细胞机制中作用的新证据。TRP 经典通道 6（TRPC6）正成为免疫相关细胞和靶组织中钙电流控制的功能元件。事实上，TRPC6 影响白细胞的任务，如跨内皮迁移、趋化性、吞噬作用和细胞因子释放。TRPC6 还调节免疫细胞对凋亡的敏感性，并影响组织对缺血再灌注损伤和兴奋性毒性的易感性。在此，我们阐述离子交换与炎症之间的相互作用，重点关注免疫介导疾病的发病机制以及潜在的未来治疗意义。
