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Immunodeficiency due to defects in store-operated calcium entry

Authors


  • Preferred citation: Feske, S. 2011. Immunodeficiency due to defects in store-operated calcium entry. In “The Year in Human and Medical Genetics: Inborn Errors of Immunity I.” Jean-Laurent Casanova, Mary Ellen Conley & Luigi Notarangelo, Eds. Ann. N.Y. Acad. Sci.1238: 74–90.

Stefan Feske, M.D., Department of Pathology, Smilow Research Building 316, 550 First Avenue, New York, NY 10016. feskes01@nyumc.org

Abstract

Mutations in genes encoding the calcium-release activated calcium (CRAC) channel abolish calcium influx in cells of the immune system and cause severe congenital immunodeficiency. Patients with autosomal recessive mutations in the CRAC channel gene ORAI1, its activator stromal interaction molecule 1 (STIM1), and mice with targeted deletion of Orai1, Stim1, and Stim2 genes reveal important roles for CRAC channels in adaptive and innate immune responses to infection and in autoimmunity. Because CRAC channels have important functions outside the immune system, deficiency of either ORAI1 or STIM1 is associated with a unique clinical phenotype. This review will give an overview of CRAC channel function in the immune system, examine the consequences of CRAC channel deficiency for immunity in human patients and mice, and discuss genetic defects in immunoreceptor-associated signaling molecules that compromise calcium influx and cause immunodeficiency.

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