Exogenous cathepsin G upregulates cell surface MHC class I molecules on immune and glioblastoma cells
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Date
2016-10-28
Authors
Giese, Madleen
Turiello, Nadine
Molenda, Nicole
Palesch, David
Meid, Annika
Schroeder, Roman
Basilico, Paola
Benarafa, Charaf
Halatsch, Marc-Eric
Zimecki, Michal
Journal Title
Journal ISSN
Volume Title
Publisher
Oncotarget
Abstract
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
Description
Keywords
cathepsin G, MHC class I, glioblastoma stem cells, lactoferrin, CatG deficient mice, Immunology and Microbiology Section, Immune response, Immunity
Citation
Madleen Giese, Nadine Turiello, Nicole Molenda, David Palesch, Annika Meid, Roman Schroeder, Paola Basilico, Charaf Benarafa, Marc-Eric Halatsch, Michal Zimecki, Mike-Andrew Westhoff, Christian Rainer Wirtz and Timo Burste. 2016. Exogenous cathepsin G upregulates cell surface MHC class I molecules on immune and glioblastoma cells. Oncotarget.