Ion Channels in Innate and Adaptive Immunity

Annu Rev Immunol. 2015;33:291-353. doi: 10.1146/annurev-immunol-032414-112212.

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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity / physiology*
  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Humans
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology
  • Hypersensitivity / metabolism
  • Immunity, Innate / physiology*
  • Immunologic Deficiency Syndromes / drug therapy
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / immunology
  • Immunologic Deficiency Syndromes / metabolism
  • Immunotherapy / methods
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Lymphocytes / cytology
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Molecular Targeted Therapy
  • Mutation
  • Signal Transduction

Substances

  • Calcium Channels
  • Cation Transport Proteins
  • Ion Channels