Acute upregulation of an NKG2D ligand promotes rapid reorganization of a local immune compartment with pleiotropic effects on carcinogenesis

Jessica Strid, Scott J. Roberts, Renata B. Filler, Julia M. Lewis, Bernice Y. Kwong, William Schpero, Daniel H. Kaplan, Adrian C. Hayday, Michael Girardi

Research output: Contribution to journalArticlepeer-review

186 Scopus citations

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 Vγ 5Vδ1 TCRγδ+ intraepithelial T cells and Langerhans cells, swiftly followed by epithelial infiltration by unconventional αβ T cells. Whereas local Vγ5Vδ1+ 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.

Original languageEnglish (US)
Pages (from-to)146-154
Number of pages9
JournalNature immunology
Volume9
Issue number2
DOIs
StatePublished - Feb 2008

Bibliographical note

Funding Information:
We thank R. Tigelaar, T. Silberzahn, J. Dyson, D. Oppenheim, M. Shlomchik and R. Montgomery for reagents, help and discussions. Supported by the National Cancer Institute (R01-CA102703 and P50-CA121974 to M.G.) and the Wellcome Trust (071534 to A.C.H. and J.S.).

Fingerprint Dive into the research topics of 'Acute upregulation of an NKG2D ligand promotes rapid reorganization of a local immune compartment with pleiotropic effects on carcinogenesis'. Together they form a unique fingerprint.

Cite this