title: Ion channels in innate and adaptive immunity.
abstract: Ion channels and transporters mediate the transport of charged ions across hydrophobic lipid membranes. In immune cells, divalent cations such as calcium, magnesium, and zinc have important roles as second messengers to regulate intracellular signaling pathways. By contrast, monovalent cations such as sodium and potassium mainly regulate the membrane potential, which indirectly controls the influx of calcium and immune cell signaling. Studies investigating human patients with mutations in ion channels and transporters, analysis of gene-targeted mice, or pharmacological experiments with ion channel inhibitors have revealed important roles of ionic signals in lymphocyte development and in innate and adaptive immune responses. We here review the mechanisms underlying the function of ion channels and transporters in lymphocytes and innate immune cells and discuss their roles in lymphocyte development, adaptive and innate immune responses, and autoimmunity, as well as recent efforts to develop pharmacological inhibitors of ion channels for immunomodulatory therapy.
authors: Department of Pathology.
authors: Stefan
authors: S
authors: Feske
authors: Heike
authors: H
authors: Wulff
authors: Edward Y
authors: EY
authors: Skolnik
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology*; D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate / Q000502:physiology*; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009154:Mutation; D015398:Signal Transduction
chemical_list: D015220:Calcium Channels; D027682:Cation Transport Proteins; D007473:Ion Channels
keywords: CRAC; KCa3.1; KV1.3; ORAI; STIM; TRP, T cells, B cells, macrophages, mast cells, DC, disease, therapy; calcium; chloride; ion channels; magnesium; potassium; sodium; transporters; zinc