Exogenous cathepsin G upregulates cell surface MHC class I molecules on immune and glioblastoma cells.
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.
Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany.
Madleen
M
Giese
Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany.
Nadine
N
Turiello
Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany.
Nicole
N
Molenda
Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
David
D
Palesch
Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany.
Annika
A
Meid
Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany.
Roman
R
Schroeder
Theodor Kocher Institute, University of Bern, Bern, Switzerland.|Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
Paola
P
Basilico
Theodor Kocher Institute, University of Bern, Bern, Switzerland.
Charaf
C
Benarafa
Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany.
Marc-Eric
ME
Halatsch
Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Michal
M
Zimecki
Department Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany.
Mike-Andrew
MA
Westhoff
Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany.
Christian Rainer
CR
Wirtz
Department of Neurosurgery, Ulm University Medical Center, Ulm, Germany.
Timo
T
Burster
D000818:Animals; D056649:Cathepsin G / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007107:Immune System / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D007781:Lactoferrin / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D059748:Proteolysis
D015395:Histocompatibility Antigens Class I; D007781:Lactoferrin; D056649:Cathepsin G
CatG deficient mice; Immune response; Immunity; Immunology and Microbiology Section; MHC class I; cathepsin G; glioblastoma stem cells; lactoferrin