Tissue Resident and Follicular Treg Cell Differentiation Is Regulated by CRAC Channels

    March 2019 in “ Nature Communications ”
    Martin Vaeth, Yin Hu Wang, Miriam Eckstein, Jun J. Yang, Gregg J. Silverman, Rodrigo S. Lacruz, Kasthuri Kannan, Stefan Feske
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    TLDR CRAC channels are crucial for the development and function of specialized immune cells, preventing severe inflammation and autoimmune diseases.
    The document presents a study on the importance of calcium release-activated calcium (CRAC) channels in the differentiation and function of regulatory T cells (Treg cells). The study found that calcium influx through CRAC channels, formed by STIM1 and STIM2 proteins, is essential for Treg cells to differentiate into specialized subsets such as follicular Treg (Tfr) cells and tissue-resident Treg cells. The absence of STIM1/STIM2 in Treg cells led to the development of fatal multiorgan inflammation and a broad spectrum of autoantibodies, including those causing autoimmune hemolytic anemia (AIHA). The study, which involved mice with sample sizes ranging from four to fifteen, showed that store-operated calcium entry (SOCE) through CRAC channels is critical for maintaining Treg cell identity, suppressive function, and preventing autoimmunity by regulating transcription factors, signaling pathways, and metabolic programming. The research highlights the role of calcium signaling in immune tolerance and its potential implications for treating autoimmune diseases.
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