The role of Ly49E receptor expression on murine intraepithelial lymphocytes in intestinal cancer development and progression

Cancer Immunol Immunother. 2016 Nov;65(11):1365-1375. doi: 10.1007/s00262-016-1894-6. Epub 2016 Sep 1.

Abstract

Ly49E is a member of the Ly49 family of NK receptors and is distinct from other members of this family on the basis of its structural properties, expression pattern and ligand recognition. Importantly, Ly49E receptor expression is high on small intestinal and colonic intraepithelial lymphocytes (IELs). Intestinal IELs are regulators of the mucosal immune system and contribute to front-line defense at the mucosal barrier, including anti-tumor immune response. Whereas most Ly49 receptors have MHC class-I ligands, we showed that Ly49E is instead triggered by urokinase plasminogen activator (uPA). uPA has been extensively implicated in tumor development, where increased uPA expression correlates with poor prognosis. As such, we investigated the role of Ly49E receptor expression on intestinal IELs in the anti-tumor immune response. For this purpose, we compared Ly49E wild-type mice to Ly49E knockout mice in two established tumor models: ApcMin/+-mediated and azoxymethane-induced intestinal cancer. Our results indicate that Ly49E expression on IELs does not influence the development or progression of intestinal cancer.

Keywords: Intestinal cancer; Intraepithelial lymphocyte; Ly49E; Urokinase plasminogen activator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics
  • Animals
  • Azoxymethane
  • Carcinogenesis
  • Carcinoma in Situ / chemically induced
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / immunology*
  • Disease Models, Animal
  • Epithelium / immunology*
  • Epithelium / pathology
  • Gene Expression Regulation, Neoplastic
  • Immunity, Cellular
  • Intestinal Neoplasms / chemically induced
  • Intestinal Neoplasms / genetics
  • Intestinal Neoplasms / immunology*
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • NK Cell Lectin-Like Receptor Subfamily A / genetics
  • NK Cell Lectin-Like Receptor Subfamily A / metabolism*
  • Tumor Burden
  • Urokinase-Type Plasminogen Activator / genetics
  • Urokinase-Type Plasminogen Activator / metabolism

Substances

  • Adenomatous Polyposis Coli Protein
  • Klra5 protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily A
  • adenomatous polyposis coli protein, mouse
  • Urokinase-Type Plasminogen Activator
  • Azoxymethane