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

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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.

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Abbreviations

AOM:

Azoxymethane

DSS:

Dextran sodium sulfate

IEL:

Intestinal intraepithelial lymphocyte

KO:

Knockout

uPA:

Urokinase plasminogen activator

WT:

Wild-type

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Acknowledgments

We wish to thank Prof. Ria Cornelissen and Leen Pieters (Department of Basic Medical Sciences, Ghent University, Ghent, Belgium) for their aid in immunofluorescent staining of tumor sections.

Funding

This work was supported by grants from the Foundation against Cancer, a foundation of public interest (2014-214) (G. Leclercq), by the Research Fund—Belgium (FWO) (G.0187.13N) (G. Leclercq), by the Interuniversity Attraction Pole (IUAP) grant T-Time from the Belspo Agency (Project P7/39) (B. Vandekerckhove, T. Taghon, G. Leclercq), and by the BOF of Ghent University (BOF11/GOA/005) (J. Plum, G. Leclercq, B. Vandekerckhove, T. Taghon). A. Van Acker and J. Filtjens are supported by the Institute for the Promotion of Innovation through Science and Technology Flanders (IWT-Vlaanderen). S. Taveirne and T. Kerre are supported by the FWO. D. Elewaut is supported by the Research Fund—Flanders (FWO) and the Research Council of Ghent University. D. Elewaut is also a member of a multidisciplinary research platform (MRP) of Ghent University and is supported by Interuniversity Attraction Pole (IUAP) grant Devrepair from the Belspo Agency (Project P7/07). E. Louagie is supported by Interuniversity Attraction Pole (IUAP) grant Devrepair from the Belspo Agency (Project P7/07).

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Authors and Affiliations

  1. Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, De Pintelaan 185, 9000, Ghent, Belgium

    Aline Van Acker, Jessica Filtjens, Sylvie Taveirne, Els Van Ammel, Tessa Kerre, Tom Taghon, Bart Vandekerckhove, Jean Plum & Georges Leclercq

  2. Department of Rheumatology, Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center, Ghent University, Ghent, Belgium

    Els Louagie & Dirk Elewaut

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  1. Aline Van Acker
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Correspondence to Georges Leclercq.

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Van Acker, A., Louagie, E., Filtjens, J. et al. The role of Ly49E receptor expression on murine intraepithelial lymphocytes in intestinal cancer development and progression. Cancer Immunol Immunother 65, 1365–1375 (2016). https://doi.org/10.1007/s00262-016-1894-6

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