Impact of Diverse Ion Channels on Regulatory T Cell Functions

Abstract

The population of regulatory T cells (Tregs) is critical for immunological self-tolerance and homeostasis. Proper ion regulation contributes to Treg lineage identity, regulation, and effector function. Identified ion channels include Ca2+ release-activated Ca2+, transient receptor potential, P2X, volume-regulated anion and K+ channels Kv1.3 and KCa3.1. Ion channel modulation represents a promising therapeutic approach for the treatment of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. This review summarizes studies with gene-targeted mice and pharmacological modulators affecting Treg number and function. Furthermore, participation of ion channels is illustrated and the power of future research possibilities is discussed.

Exploring the therapeutic opportunities of potassium channels for the treatment of rheumatoid arthritis

“…As discussed in Section 2.1.2 , T reg cells play a significant role in RA pathogenesis, and proper ion regulation is required for the regulation and effector function of a cell ( Varga et al, 2009 ; Kotschenreuther et al, 2022 ). T regs are critical contributors to immune tolerance, and defects in their function are associated with autoimmune diseases such as RA ( Vinnenberg et al, 2021 ). The potassium channels, such as voltage-gated K + channel Kv1.3 and calcium-activated K + channel KCa3.1, predominantly control membrane potential in T reg cells ( Vinnenberg et al, 2021 ).…”

“…T regs are critical contributors to immune tolerance, and defects in their function are associated with autoimmune diseases such as RA ( Vinnenberg et al, 2021 ). The potassium channels, such as voltage-gated K + channel Kv1.3 and calcium-activated K + channel KCa3.1, predominantly control membrane potential in T reg cells ( Vinnenberg et al, 2021 ). Both these channels are involved in the antigenic activation and proliferation of T cells, and each channel expresses differently in each T-cell subtype ( Vinnenberg et al, 2021 ).…”

“…The potassium channels, such as voltage-gated K + channel Kv1.3 and calcium-activated K + channel KCa3.1, predominantly control membrane potential in T reg cells ( Vinnenberg et al, 2021 ). Both these channels are involved in the antigenic activation and proliferation of T cells, and each channel expresses differently in each T-cell subtype ( Vinnenberg et al, 2021 ). Studies indicated the high Kv1.3 channel activity in the pathogenesis of RA, and dominant KCa3.1 channel expression was observed in Th1 cells, which is closely associated with autoimmunity ( Vinnenberg et al, 2021 ).…”

“…Both these channels are involved in the antigenic activation and proliferation of T cells, and each channel expresses differently in each T-cell subtype ( Vinnenberg et al, 2021 ). Studies indicated the high Kv1.3 channel activity in the pathogenesis of RA, and dominant KCa3.1 channel expression was observed in Th1 cells, which is closely associated with autoimmunity ( Vinnenberg et al, 2021 ). Similar to T regs , DCs are involved in the progression of RA as they are specialized APCs and are engaged in both specific immunity and immune tolerance ( Veldhoen et al, 2006 ; Wehr et al, 2019 ).…”

“…Ion channels came into the limelight for the treatment of autoimmune diseases as ion channels have the ability to establish membrane potential, ion concentration, and regulate immune response in immune cells ( Chandy et al, 1985 ; Vinnenberg et al, 2021 ). Genetic alterations in ion channels contribute to the pathogenesis of several diseases.…”