Chloride Channel Expression and Functional Diversity in the Immune Cells of Allergic Diseases

Abstract

Chloride channels are involved in many different physiological processes such as cell migration, proliferation and apoptosis. The importance of the CLC family of chloride channels in these cellular functions has been recognized only recently. Infiltration of inflammatory cells, such as eosinophils, T cells, mast cells and neutrophils, is a hallmark of allergy and asthma. Indeed, chronic asthma is associated with widespread damage to the bronchial epithelium, due to excessive apoptosis, and with defective epithelial repair. However, the relationship between the immune cells of allergic airway diseases and chloride channels has not been clearly elucidated. In this review, characteristics of CLC channels are mainly discussed based on their function and presence in different immune cells in airway diseases. Not only are chloride channels involved in the recruitment of immune cells, they also play a role in the activation of these cells. Thus, understanding the role of CLC channels in the immune cells would provide unique insights to the pathophysiologic process of chronic asthma and the means to prevent or reverse the disease.

γ-Aminobutyric Acid Transporter 1 Negatively Regulates T Cell Activation and Survival through Protein Kinase C-Dependent Signaling Pathways

“…For example, because GAT-1 belongs to the Na ϩ -and Cl Ϫ -dependent transporter family solute carrier family 6, its activation might induce Cl Ϫ flux. Previous studies have revealed that Cl Ϫ channels are widely involved in physiological processes such as cell proliferation, apoptosis and migration (38). Therefore, it is necessary to investigate whether Cl Ϫ flux is involved in GAT-1 mediated T cell activation.…”

Clcn5 Knockout Mice Exhibit Novel Immunomodulatory Effects and Are More Susceptible to Dextran Sulfate Sodium-Induced Colitis

“…proteinuria, aminoaciduria, glycosuria, phosphaturia, hypercalciuria, nephrolithiasis, and progressive renal failure (27–35). In general, CLC channels have been demonstrated to contribute to a host of biological and cellular processes, including cell migration, proliferation, and apoptosis (36). Only CLC-3 has been shown to play a critical role in TGF-β–induced apoptosis of human airway epithelial cells and has recently been shown to be involved in the recruitment and activation of immune cells in the respiratory tract (36, 37).…”

“…In general, CLC channels have been demonstrated to contribute to a host of biological and cellular processes, including cell migration, proliferation, and apoptosis (36). Only CLC-3 has been shown to play a critical role in TGF-β–induced apoptosis of human airway epithelial cells and has recently been shown to be involved in the recruitment and activation of immune cells in the respiratory tract (36, 37). However, the specific role of CLC-5 and/or cellular mediators that modulate important immune functions to trigger downstream signaling pathways has not yet been defined.…”

Intermediate-conductance calcium-activated potassium channel KCa3.1 and chloride channel modulate chemokine ligand (CCL19/CCL21)-induced migration of dendritic cells

“…Volume sensitive chloride channel CLC3 is involved in neutrophil [35] migration, but the detailed underlying mechanism still has not yet been deciphered [36]. Moreover, chloride and potassium channels might work in concert with each other [37] in order to achieve the optimal volume change in cell migration [10].…”