Cathepsin G and its Dichotomous Role in Modulating Levels of MHC Class I Molecules
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(2020) 68:25
REVIEW
Cathepsin G and its Dichotomous Role in Modulating Levels of MHC Class I Molecules Timo Burster1 · Uwe Knippschild2 · Ferdinand Molnár1 · Anuar Zhanapiya1 Received: 30 November 2019 / Accepted: 11 June 2020 © L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2020
Abstract Cathepsin G (CatG) is involved in controlling numerous processes of the innate and adaptive immune system. These features include the proteolytic activity of CatG and play a pivotal role in alteration of chemokines as well as cytokines, clearance of exogenous and internalized pathogens, platelet activation, apoptosis, and antigen processing. This is in contrast to the capability of CatG acting in a proteolytic-independent manner due to the net charge of arginine residues in the CatG sequence which interferes with bacteria. CatG is a double-edged sword; CatG is also responsible in pathophysiological conditions, such as autoimmunity, chronic pulmonary diseases, HIV infection, tumor progression and metastasis, photo-aged human skin, Papillon–Lefèvre syndrome, and chronic inflammatory pain. Here, we summarize the latest findings for functional responsibilities of CatG in immunity, including bivalent regulation of major histocompatibility complex class I molecules, which underscore an additional novel role of CatG within the immune system. Keywords Cathepsin G · Proteases · T regulatory cells · NK cells · MHC · Lactoferrin · Protease-activated receptor Abbreviations APCs Antigen-presenting cells Cat Cathepsin CatG Cathepsin G cDCs Conventional dendritic cells DCs Dendritic cells HIV Human immunodeficiency virus HLA Human leukocyte antigen LF Lactoferrin MHC Major histocompatibility complex NE Neutrophil elastase NETs Neutrophil extracellular traps NK Natural killer PAR Protease-activated receptor PBMCs Peripheral blood mononuclear cells PMSF Phenylmethylsulfonyl fluoride SDF1 Stromal cell-derived factor 1 TCR T cell receptor * Timo Burster [email protected] 1
Department of Biology, School of Sciences and Humanities, Nazarbayev University, Kabanbay Batyr Ave. 53, Nur‑Sultan 010000, Kazakhstan
Department of General and Visceral Surgery, Surgery Center, Ulm University Hospital, 89081 Ulm, Germany
2
TGF-β Transforming growth factor beta Th T helper Tregs T regulatory cells Tregs Thymus-derived natural Tregs T1D Type 1 diabetes mellitus
Introduction Proteases are proteolytic enzymes that participate in physiological cell metabolism and are mainly responsible for protein degradation by hydrolysis. As a consequence, they are functional in the immune system, for instance, for processing of intracellular antigens within antigen-presenting cells (APCs) (Kramer et al. 2017; Sadeghzadeh et al. 2020). Neutrophils, recruited and activated at the site of inflammation, naturally release different classes of mediators to the surrounding environment and thereby support an immune response. One example is serine proteases, such as cathepsin G (CatG), protease 3 (PR3), neutrophil el
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