期刊
NATURE IMMUNOLOGY
卷 9, 期 2, 页码 146-154出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni1556
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- Medical Research Council [G0600698B] Funding Source: researchfish
- NCI NIH HHS [R01-CA102703] Funding Source: Medline
- Wellcome Trust [085780, 071534] Funding Source: Medline
The self-encoded ligands MICA ( human) and Rae-1 ( mouse) for the cytotoxic lymphocyte activating receptor NKG2D are highly expressed in carcinomas and inflammatory lesions and have been linked to immunosurveillance and graft rejection. However, whether NKG2D ligands have an intrinsic ability to acutely regulate tissue-associated immune compartments is not known. Here we show that epidermis-specific upregulation of Rae-1 induced rapid, coincident and reversible changes in the organization of tissue-resident V gamma 5V delta 1 TCR gamma delta(+) intraepithelial T cells and Langerhans cells, swiftly followed by epithelial infiltration by unconventional ab T cells. Whereas local V gamma 5V delta 1(+) T cells limited carcinogenesis, Langerhans cells unexpectedly promoted it. These results provide unique insight into the early phases of tissue immunosurveillance and indicate that acute changes in NKG2D ligands may alone initiate a rapid, multifaceted immunosurveillance response in vivo.
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