Distinct Spatial and Molecular Features of Notch Pathway Assembly in Regulatory T Cells

doi:10.1126/scisignal.2002859

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Sci. Signal., 24 July 2012
Vol. 5, Issue 234, p. ra53
[DOI: 10.1126/scisignal.2002859]

RESEARCH ARTICLES

Editor's Summary

Cytosolic Notch Protects T Cells

Effector T cells direct the immune response against pathogens, whereas regulatory T cells (T_regs) suppress effector T cell function to keep the immune response in check. In addition to their opposing functions, these cells have different responses when survival cytokines are unavailable. Effector T cells undergo apoptosis, whereas T_regs survive (see the Perspective by Minter and Osborne). Perumalsamy et al. found that the differential survival of effector T cells and T_regs correlated with differential signaling by the receptor Notch1. Whereas the Notch1 intracellular domain (NICD) was localized to the nucleus in effector T cells, it was localized in the cytosol of T_regs, and blockade of Notch1 signaling or prevention of the cytosolic localization of NICD abolished the protection of T_regs from apoptosis. T_reg survival depended on interactions between Notch1 and components of the phosphatidylinositol 3-kinase and mammalian target of rapamycin signaling pathways. Together, these data implicate spatial control of Notch signaling components in the protection of specific T cell subsets from apoptosis.

Citation: L. R. Perumalsamy, N. Marcel, S. Kulkarni, F. Radtke, A. Sarin, Distinct Spatial and Molecular Features of Notch Pathway Assembly in Regulatory T Cells. Sci. Signal. 5, ra53 (2012).

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:

Notch and the Survival of Regulatory T Cells: Location Is Everything!.: L. M. Minter and B. A. Osborne (2012)
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