title: 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.
authors.affiliation: Department of Pathology, New York University Medical Center, 550 First Avenue, SRB 316, New York, NY 10016, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Shaw
authors.forename: Stefan
authors.initials: S
authors.lastname: Feske
mesh_terms: D000818:Animals; D015551:Autoimmunity; D015220:Calcium Channels / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D020013:Calcium Signaling; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007239:Infections / Q000276:immunology* / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation
chemical_list: D015220:Calcium Channels; D008562:Membrane Glycoproteins