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Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance

Masatsugu Oh-Hora1, Megumi Yamashita, Patrick G Hogan

  • 1Harvard Medical School and Immune Disease Institute, Boston, Massachusetts 02115, USA.

Nature Immunology
|March 11, 2008
PubMed

Insights

Stromal interaction molecule (STIM) proteins are crucial for calcium influx in immune cells. Both STIM1 and STIM2 are essential for T cell function, development, and regulatory T cell populations.

Area of Science:

  • Immunology
  • Cell Biology
  • Calcium Signaling

Background:

  • Store-operated Ca2+ entry is vital for immune cell function, primarily mediated by calcium release-activated calcium channels.
  • Stromal interaction molecule (STIM) proteins act as calcium sensors regulating this process.

Purpose of the Study:

  • To investigate the distinct and overlapping roles of STIM1 and STIM2 in T cells and fibroblasts.
  • To determine the necessity of STIM proteins for T cell activation, cytokine production, and regulatory T cell homeostasis.

Main Methods:

  • Utilized knockout mouse models lacking STIM1 and/or STIM2 in T cells and fibroblasts.
  • Assessed store-operated Ca2+ influx, cytokine production, nuclear factor of activated T cells (NFAT) translocation, and T cell populations.

Main Results:

  • STIM1 deficiency severely impaired store-operated Ca2+ influx in T cells and fibroblasts; STIM2 deficiency had a lesser impact.
  • T cells lacking either STIM1 or STIM2 exhibited reduced cytokine production and NFAT nuclear translocation.
  • Combined ablation of STIM1 and STIM2 in T cells led to lymphoproliferation and a significant decrease in regulatory T cell numbers.

Conclusions:

  • Both STIM1 and STIM2 are important for store-operated Ca2+ entry in T cells and fibroblasts.
  • STIM proteins are indispensable for the development and function of regulatory T cells, impacting their numbers and overall T cell homeostasis.

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