期刊
NATURE IMMUNOLOGY
卷 16, 期 11, 页码 1162-1173出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3288
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资金
- US National Institutes of Health [2R01AI065617, 2R01AI085090, 1R56AI115699-01]
Receptors of the Notch family direct the differentiation of helper T cell subsets, but their influence on regulatory T cell (T-reg cell) responses is obscure. We found here that lineage-specific deletion of components of the Notch pathway enhanced Treg cell mediated suppression of type 1 helper T cell (T(H)1 cell) responses and protected against their T(H)1 skewing and apoptosis. In contrast, expression in Tin cells of a gain-of-function transgene encoding the Notchl intracellular domain resulted in lymphoproliferation, exacerbated T(H)1 responses and autoimmunity. Cell-intrinsic canonical Notch signaling impaired Treg cell fitness and promoted the acquisition by Treg cells of a T(H)1 cell like phenotype, whereas non-canonical Notch signaling dependent on the adaptor Rictor activated the kinase AKT-transcription factor Foxo1 axis and impaired the epigenetic stability of Foxp3. Our findings establish a critical role for Notch signaling in controlling peripheral T-reg cell function.
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