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.

The potassium channel KCa3.1 constitutes a pharmacological target for neuroinflammation associated with ischemia/reperfusion stroke

“…[9][10][11] Both channels are also expressed in monocyte-derived macrophages. 12 Similar to findings in T cells, where the roles of Kv1.3 and KCa3.1 have been studied in great detail, the channels regulate membrane potential and Ca 2þ signaling in microglia and monocyte-derived macrophages. 12 However, most previous studies have been performed with cultured neonatal mouse or rat microglia, 13 and it has been questioned whether these systems correctly represent microglia in vivo.…”

7DHC-induced changes of Kv1.3 operation contributes to modified T cell function in Smith-Lemli-Opitz syndrome

“…Also, the Blong-term effect^of modified operation of ion channels could be traced with the proliferation assay: SLOS cells tended to divide at a lower rate compared to control T cells, a phenomenon which was clearly shown for Kv1.3 inhibitors [10,63]. The Ca 2+ -signaling-linked activation of T lymphocytes is a classic example of the interplay of ion channels, transporters, and signaling molecules (see above), reviewed in [22,64]. Even though the sterol sensitivity of Kv1.3 is a potential mechanism for the reduced T cell activation/proliferation, we cannot exclude that the altered lipid milieu in SLOS affects other transporters and/or signaling molecules, which contribute to the altered T cell function in SLOS.…”

STIM1 controls T cell–mediated immune regulation and inflammation in chronic infection

“…2+ concentrations is an important mechanism for regulating the function of many immune cells, especially T cells (1). In response to antigen binding to the T cell receptor (TCR), Ca 2+ is released from ER stores.…”