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Exogenous cathepsin G upregulates cell surface MHC class I molecules on immune and glioblastoma cells
- Source :
- Oncotarget
- Publication Year :
- 2016
-
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.
- Subjects :
- 0301 basic medicine
Male
Cathepsin G
Antigen presentation
CD1
chemical and pharmacologic phenomena
Biology
Major histocompatibility complex
Monocytes
Cell Line
03 medical and health sciences
Mice
0302 clinical medicine
Antigen
Cell Line, Tumor
MHC class I
Cytotoxic T cell
Animals
Humans
Immune response
Mice, Knockout
glioblastoma stem cells
CatG deficient mice
Cell Membrane
Histocompatibility Antigens Class I
Research Paper: Immunology
Immunity
MHC restriction
Acquired immune system
Molecular biology
3. Good health
Cell biology
lactoferrin
Gene Expression Regulation, Neoplastic
Disease Models, Animal
030104 developmental biology
Oncology
Immune System
Proteolysis
biology.protein
Neoplastic Stem Cells
Immunology and Microbiology Section
Female
Glioblastoma
030215 immunology
Subjects
Details
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....a9167222c429223fd46908b71707b6d2