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


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

3 Figures and Tables

Citations per Year

229 Citations

Semantic Scholar estimates that this publication has 229 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@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} }