Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance.
Store-operated Ca2+ entry through calcium release-activated calcium channels is the chief mechanism for increasing intracellular Ca2+ in immune cells. Here we show that mouse T cells and fibroblasts lacking the calcium sensor STIM1 had severely impaired store-operated Ca2+ influx, whereas deficiency in the calcium sensor STIM2 had a smaller effect. However, T cells lacking either STIM1 or STIM2 had much less cytokine production and nuclear translocation of the transcription factor NFAT. T cell-specific ablation of both STIM1 and STIM2 resulted in a notable lymphoproliferative phenotype and a selective decrease in regulatory T cell numbers. We conclude that both STIM1 and STIM2 promote store-operated Ca2+ entry into T cells and fibroblasts and that STIM proteins are required for the development and function of regulatory T cells.
Oh-Hora
Masatsugu
M
Harvard Medical School and Immune Disease Institute, Boston, Massachusetts 02115, USA.
Yamashita
Megumi
M
Hogan
Patrick G
PG
Sharma
Sonia
S
Lamperti
Ed
E
Chung
Woo
W
Prakriya
Murali
M
Feske
Stefan
S
Rao
Anjana
A
D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active / Q000235:genetics / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015220:Calcium Channels; D008562:Membrane Glycoproteins; C100757:Stim1 protein, mouse; C525024:Stim2 protein, mouse; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D002118:Calcium