Acute upregulation of an NKG2D ligand promotes rapid reorganization of a local immune compartment with pleiotropic effects on carcinogenesis.
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 TCRgammadelta+ intraepithelial T cells and Langerhans cells, swiftly followed by epithelial infiltration by unconventional alphabeta 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.
Strid
Jessica
J
Peter Gorer Department of Immunobiology, King's College London School of Medicine at Guy's Hospital, London SE1 9RT, UK.
Roberts
Scott J
SJ
Filler
Renata B
RB
Lewis
Julia M
JM
Kwong
Bernice Y
BY
Schpero
William
W
Kaplan
Daniel H
DH
Hayday
Adrian C
AC
Girardi
Michael
M
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D004817:Epidermis / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007157:Immunologic Surveillance; D007801:Langerhans Cells / Q000276:immunology*; D008024:Ligands; D051379:Mice; D008815:Mice, Inbred Strains; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D012878:Skin Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation
D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell