Perišić Nanut Milica, Pečar Fonović Urša, Jakoš Tanja, Kos Janko
Department of Biotechnology, Jožef Stefan Institute, Ljubljana, Slovenia.
Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
Front Immunol. 2021 Jul 15;12:680279. doi: 10.3389/fimmu.2021.680279. eCollection 2021.
Cysteine cathepsins are primarily involved in the degradation and recycling of proteins in endo-lysosomal compartments but are also gaining recognition as pivotal proteolytic contributors to various immune functions. Through their extracellular proteolytic activities within the hematopoietic stem cell niche, they are involved in progenitor cell mobilization and differentiation. Cysteine cathepsins, such as cathepsins L and S contribute to antigen-induced adaptive immunity through major histocompatibility complex class II antigen presentation whereas cathepsin X regulates T-cell migration. By regulating toll-like receptor signaling and cytokine secretion cysteine cathepsins activate innate immune cells and affect their functional differentiation. Cathepsins C and H are expressed in cytotoxic T lymphocytes and natural killer cells and are involved in processing of pro-granzymes into proteolytically active forms. Cytoplasmic activities of cathepsins B and L contribute to the maintenance of homeostasis of the adaptive immune response by regulating cell death of T and B lymphocytes. The expression pattern, localization, and activity of cysteine cathepsins is tightly connected to their function in immune cells. Furthermore, cysteine cathepsins together with their endogenous inhibitors, serve as mediators in the interplay between cancer and immune cells that results in immune cell anergy. The aim of the present article is to review the mechanisms of dysregulation of cysteine cathepsins and their inhibitors in relation to immune dysfunction to address new possibilities for regulation of their function.
半胱氨酸组织蛋白酶主要参与内溶酶体区室中蛋白质的降解和循环利用，但作为各种免疫功能的关键蛋白水解因子也日益受到认可。通过其在造血干细胞龛内的细胞外蛋白水解活性，它们参与祖细胞的动员和分化。半胱氨酸组织蛋白酶，如组织蛋白酶L和S，通过主要组织相容性复合体II类抗原呈递促进抗原诱导的适应性免疫，而组织蛋白酶X调节T细胞迁移。通过调节Toll样受体信号传导和细胞因子分泌，半胱氨酸组织蛋白酶激活先天免疫细胞并影响其功能分化。组织蛋白酶C和H在细胞毒性T淋巴细胞和自然杀伤细胞中表达，并参与将前颗粒酶加工成蛋白水解活性形式。组织蛋白酶B和L的细胞质活性通过调节T和B淋巴细胞的细胞死亡，有助于维持适应性免疫反应的稳态。半胱氨酸组织蛋白酶的表达模式、定位和活性与其在免疫细胞中的功能紧密相关。此外，半胱氨酸组织蛋白酶与其内源性抑制剂一起，在癌症与免疫细胞之间的相互作用中充当介质，导致免疫细胞无反应性。本文的目的是综述半胱氨酸组织蛋白酶及其抑制剂失调与免疫功能障碍相关的机制，以探讨调节其功能的新可能性。
