Impact of Diverse Ion Channels on Regulatory T Cell Functions

Cell Physiol Biochem. 2021 May 28;55(S3):145-156. doi: 10.33594/000000375.

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.

Keywords: Tregs; Ion channels; CRAC; Kv1.3; KCa3.1; TRP; P2X; VRAC.

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Calcium / immunology
  • Calcium / metabolism*
  • Calcium Release Activated Calcium Channels / genetics
  • Calcium Release Activated Calcium Channels / immunology
  • Calcium Signaling
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / immunology
  • Humans
  • Intermediate-Conductance Calcium-Activated Potassium Channels / genetics
  • Intermediate-Conductance Calcium-Activated Potassium Channels / immunology
  • Kv1.3 Potassium Channel / genetics
  • Kv1.3 Potassium Channel / immunology
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Transport Modulators / chemistry
  • Membrane Transport Modulators / pharmacology*
  • Mice
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism
  • Receptors, Purinergic P2X / genetics
  • Receptors, Purinergic P2X / immunology
  • Receptors, Purinergic P2X7 / genetics
  • Receptors, Purinergic P2X7 / immunology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology
  • Transient Receptor Potential Channels / genetics
  • Transient Receptor Potential Channels / immunology

Substances

  • Calcium Release Activated Calcium Channels
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • Kcnn4 protein, mouse
  • Kv1.3 Potassium Channel
  • LRRC8A protein, mouse
  • Membrane Proteins
  • Membrane Transport Modulators
  • P2rx7 protein, mouse
  • Receptors, Purinergic P2X
  • Receptors, Purinergic P2X7
  • Transient Receptor Potential Channels
  • Calcium