title: Cysteine cathepsins as regulators of the cytotoxicity of NK and T cells.
abstract: Cysteine cathepsins are lysosomal peptidases involved at different levels in the processes of the innate and adaptive immune responses. Some, such as cathepsins B, L, and H are expressed constitutively in most immune cells. In cells of innate immunity they play a role in cell adhesion and phagocytosis. Other cysteine cathepsins are expressed more specifically. Cathepsin X promotes dendritic cell maturation, adhesion of macrophages, and migration of T cells. Cathepsin S is implicated in major histocompatibility complex class II antigen presentation, whereas cathepsin C, expressed in cytotoxic T lymphocytes and natural killer (NK) cells, is involved in processing pro-granzymes into proteolytically active forms, which trigger cell death in their target cells. The activity of cysteine cathepsins is controlled by endogenous cystatins, cysteine protease inhibitors. Of these, cystatin F is the only cystatin that is localized in endosomal/lysosomal vesicles. After proteolytic removal of its N-terminal peptide, cystatin F becomes a potent inhibitor of cathepsin C with the potential to regulate pro-granzyme processing and cell cytotoxicity. This review is focused on the role of cysteine cathepsins and their inhibitors in the molecular mechanisms leading to the cytotoxic activity of T lymphocytes and NK cells in order to address new possibilities for regulation of their function in pathological processes.
authors.affiliation: Department of Biotechnology, Jožef Stefan Institute , Ljubljana , Slovenia.
authors.forename: Milica
authors.initials: M
authors.lastname: Perišić Nanut
authors.affiliation: Department of Biotechnology, Jožef Stefan Institute , Ljubljana , Slovenia.
authors.forename: Jerica
authors.initials: J
authors.lastname: Sabotič
authors.affiliation: Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, University of California Los Angeles , Los Angeles, CA , USA.
authors.forename: Anahid
authors.initials: A
authors.lastname: Jewett
authors.affiliation: Department of Biotechnology, Jožef Stefan Institute , Ljubljana , Slovenia ; Faculty of Pharmacy, University of Ljubljana , Ljubljana , Slovenia.
authors.forename: Janko
authors.initials: J
authors.lastname: Kos
keywords: cathepsins; cystatins; cytotoxic T cells; cytotoxicity; natural killer cells