Article abstract
Nature Immunology 9, 146 - 154 (2008)
Published online: 6 January 2008 | doi:10.1038/ni1556
Acute upregulation of an NKG2D ligand promotes rapid reorganization of a local immune compartment with pleiotropic effects on carcinogenesis
Jessica Strid1, Scott J Roberts2, Renata B Filler2, Julia M Lewis2, Bernice Y Kwong2, William Schpero2, Daniel H Kaplan3, Adrian C Hayday1,4 & Michael Girardi2,4
Abstract
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
5V
1 TCR
+ intraepithelial T cells and Langerhans cells, swiftly followed by epithelial infiltration by unconventional 
T cells. Whereas local V5V1+ 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.
- Peter Gorer Department of Immunobiology, King's College London School of Medicine at Guy's Hospital, London SE1 9RT, UK.
- Department of Dermatology and Skin Diseases Research Center, Yale University School of Medicine, New Haven, Connecticut 06511, USA.
- Department of Dermatology and Center for Immunology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
- These authors contributed equally to this work.
Correspondence to: Adrian C Hayday1,4 e-mail: adrian.hayday@kcl.ac.uk
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