Article abstract
Nature Immunology 9, 424 - 431 (2008)
Published online: 16 March 2008 | doi:10.1038/ni1570
Regulation of T cell survival through coronin-1–mediated generation of inositol-1,4,5-trisphosphate and calcium mobilization after T cell receptor triggering
Philipp Mueller1,4, Jan Massner1,4, Rajesh Jayachandran1,4, Benoit Combaluzier1, Imke Albrecht1, John Gatfield1, Carmen Blum2, Rod Ceredig3, Hans-Reimer Rodewald2, Antonius G Rolink3 & Jean Pieters1
Abstract
T cell homeostasis is essential for the functioning of the vertebrate immune system, but the intracellular signals required for T cell homeostasis are largely unknown. We here report that the WD-repeat protein family member coronin-1, encoded by the gene Coro1a, is essential in the mouse for T cell survival through its promotion of Ca2+ mobilization from intracellular stores. Upon T cell receptor triggering, coronin-1 was essential for the generation of inositol-1,4,5-trisphosphate from phosphatidylinositol-4,5-bisphosphate. The absence of coronin-1, although it did not affect T cell development, resulted in a profound defect in Ca2+ mobilization, interleukin-2 production, T cell proliferation and T cell survival. We conclude that coronin-1, through activation of Ca2+ release from intracellular stores, is an essential regulator of peripheral lymphocyte survival.
- Biozentrum, University of Basel, Klingelbergstrasse 50-70, CH 4056 Basel, Switzerland.
- Institute for Immunology, University of Ulm, Germany.
- Department of Clinical Biological Sciences, University of Basel, Mattenstrasse 28, CH 4058 Basel, Switzerland.
- These authors contributed equally to this work.
Correspondence to: Jean Pieters1 e-mail: jean.pieters@unibas.ch
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