Exogenous cathepsin G upregulates cell surface MHC class I molecules on immune and glioblastoma cells.

Giese, Madleen; Turiello, Nadine; Molenda, Nicole; Palesch, David; Meid, Annika; Schroeder, Roman; Basilico, Paola; Benarafa, Charaf; Halatsch, Marc-Eric; Zimecki, Michal; Westhoff, Mike-Andrew; Wirtz, Christian Rainer; Burster, Timo (2016). Exogenous cathepsin G upregulates cell surface MHC class I molecules on immune and glioblastoma cells. OncoTarget, 7(46), pp. 74602-74611. Impact Journals LLC 10.18632/oncotarget.12980

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Major histocompatibility complex (MHC) class I molecules present antigenic peptides to cytotoxic T cells. During an adaptive immune response, MHC molecules are regulated by several mechanisms including lipopolysaccharide (LPS) and interferon gamma (IFN-g). However, it is unclear whether the serine protease cathepsin G (CatG), which is generally secreted by neutrophils at the site of inflammation, might regulate MHC I molecules. We identified CatG, and to a higher extend CatG and lactoferrin (LF), as an exogenous regulator of cell surface MHC I expression of immune cells and glioblastoma stem cells. In addition, levels of MHC I molecules are reduced on dendritic cells from CatG deficient mice compared to their wild type counterparts. Furthermore, cell surface CatG on immune cells, including T cells, B cells, and NK cells triggers MHC I on THP-1 monocytes suggesting a novel mechanism for CatG to facilitate intercellular communication between infiltrating cells and the respective target cell. Subsequently, our findings highlight the pivotal role of CatG as a checkpoint protease which might force target cells to display their intracellular MHC I:antigen repertoire.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Basilico, Paola and Benarafa, Charaf

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1949-2553

Publisher:

Impact Journals LLC

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

22 May 2017 14:09

Last Modified:

22 May 2017 14:17

Publisher DOI:

10.18632/oncotarget.12980

PubMed ID:

27806341

Uncontrolled Keywords:

CatG deficient mice; Immune response; Immunity; Immunology and Microbiology Section; MHC class I; cathepsin G; glioblastoma stem cells; lactoferrin

BORIS DOI:

10.7892/boris.95400

URI:

https://boris.unibe.ch/id/eprint/95400

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