Regulation of lymphocyte function by ORAI and STIM proteins in infection and autoimmunity.

Abstract

Store-operated Ca(2+) entry (SOCE) in cells of the immune system is mediated by Ca(2+) release-activated Ca(2+) (CRAC) channels that are formed by ORAI1 and its homologues ORAI2 and ORAI3. They are activated by stromal interaction molecules (STIM) 1 and 2 in response to depletion of endoplasmic reticulum Ca(2+) stores. Loss-of-function mutations in the human ORAI1 and STIM1 genes abolish CRAC channel function and SOCE in a variety of non-excitable cells including lymphocytes and other immune cells, resulting in a unique clinical syndrome termed CRAC channelopathy. It is dominated by severe immunodeficiency and autoimmunity due to impaired SOCE and defects in the function of several lymphocyte subsets. These include CD8(+) T cells, CD4(+) effector and regulatory T cells, natural killer (NK) cells and B cells. This review provides a concise discussion of the role of CRAC channels in these lymphocyte populations and the regulation of adaptive immune responses to infection, in autoimmunity and inflammation.

DOI: 10.1113/jphysiol.2012.233221

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@article{Shaw2012RegulationOL, title={Regulation of lymphocyte function by ORAI and STIM proteins in infection and autoimmunity.}, author={Patrick Shaw and Stefan Feske}, journal={The Journal of physiology}, year={2012}, volume={590 17}, pages={4157-67} }