CRAC Channels and Calcium Signaling in T Cell-Mediated Immunity

Abstract

Calcium (Ca²⁺) signals play fundamental roles in immune cell function. The main sources of Ca²⁺ influx in mammalian lymphocytes following antigen receptor stimulation are Ca²⁺ release-activated Ca²⁺ (CRAC) channels. These are formed by ORAI proteins in the plasma membrane and are activated by stromal interaction molecules (STIM) located in the endoplasmic reticulum (ER). Human loss-of-function (LOF) mutations in ORAI1 and STIM1 that abolish Ca²⁺ influx cause a unique disease syndrome called CRAC channelopathy that is characterized by immunodeficiency autoimmunity and non-immunological symptoms. Studies in mice lacking Stim and Orai genes have illuminated many cellular and molecular mechanisms by which these molecules control lymphocyte function. CRAC channels are required for the differentiation and function of several T lymphocyte subsets that provide immunity to infection, mediate inflammation and prevent autoimmunity. This review examines new insights into how CRAC channels control T cell-mediated immunity.

Keywords: CRAC channel; Calcium; Lymphocyte; ORAI; STIM; T cell.