REVIEW article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1600206
This article is part of the Research TopicCellular and Molecular Regulators in Non-neoplastic Immune-mediated DiseasesView all 6 articles
Cathepsin S: Molecular Mechanisms in Inflammatory and Immunological Processes
Provisionally accepted
- 1The Central Laboratory of the First Hospital of Jilin University, Changchun, China
- 2Jilin university, Changchun, China
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Cathepsin S (CTSS), a lysosomal cysteine protease predominantly expressed in immune cells, governs inflammatory and immunological cascades through proteolytic activity. Beyond maintaining lysosomal proteostasis through protein degradation, CTSS executes dual immunomodulatory functions: intracellularly processing antigen-presenting molecules and modulating inflammatory signaling cascades; extracellularly activating protease-activated receptors (PARs) and remodeling the extracellular matrix (ECM). Its dysregulation drives pathology in autoimmune disorders, chronic inflammation, and neoplasia, establishing CTSS as a multifaceted therapeutic target. This review comprehensively explores the contributions of CTSS signaling in immune-mediated inflammatory diseases, critically evaluates its therapeutic potential, highlighting its significance in the development of innovative treatment strategies.1 Introduction Inflammation represents a critical pathophysiological response to diverse stimuli including infections, tissue injury, cellular stress, and chemical agents. Immune cells orchestrate inflammatory processes through coordinated mechanisms: circulating leukocytes infiltrate damaged tissues, while resident macrophages modulate local inflammatory dynamics (1). Pathological inflammation underlies diseases, ranging from immune-mediated disorders (such as multiple sclerosis and Crohn's disease) to cardiovascular pathologies (e.g., atherosclerosis), neurodegenerative conditions (e.g., Alzheimer's disease), and psychiatric disorders (e.g., generalized anxiety disorder) (2-9). Within cellular microenvironments, inflammatory signaling is regulated by lysosome-dependent mechanisms, where macrophages and dendritic cells (DCs) employ lysosomal enzymes as key effectors (10). Among these, cathepsins (CTSs) mediate inflammatory signal transduction through their proteolytic processing of intracellular and extracellular proteins.Cathepsin S (CTSS), a lysosomal cysteine protease, uniquely maintains enzymatic activity at neutral pH (≤7) due to its histidine-rich propeptide domain, distinguishing it from acid-dependent cathepsins (e.g., Cathepsin B/L/K) (11). This property enables CTSS to perform both intra-and
Keywords: cathepsin S (ctss), molecular mechanism, Immunoregulation, inflammatory disease, therapeutic targets
Received: 26 Mar 2025; Accepted: 16 Jun 2025.
Copyright: © 2025 Gao, Zhang, Deng and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Huan Gao, The Central Laboratory of the First Hospital of Jilin University, Changchun, China
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