CD57的分子特征、在T细胞和NK细胞亚群中的差异化表达与功能、在生理性免疫老化中 的意义及其在多种疾病状态下的 临床相关性

Molecular Characteristics of CD57, Differential Expression and Functional Profiles across T-Cell and NK-Cell Subsets, Implications in Physiological Immune Aging, and Clinical Correlations in Diverse Disease Contexts

摘要: CD57是最早被鉴定的人类自然杀伤(natural killer, NK)细胞表面标志物之一，长期以来被认为是淋巴细胞终末分化和免疫衰老的重要表型标志。近年来，随着单细胞测序、多参数流式细胞术、空间转录组学等技术的发展，CD57的生物学意义得到了重新认识，其功能已从单纯的免疫衰老标志扩展为参与淋巴细胞分化、功能调控及免疫稳态维持的重要分子。本文系统综述了CD57的分子结构和生物学特性，重点总结了CD57在NK细胞、T细胞及NKT样细胞等淋巴细胞亚群中的差异化表达模式及功能特征，并进一步分析了CD57⁺淋巴细胞在不同免疫微环境中表现出的功能异质性及其潜在分子调控机制。本文还阐述了CD57⁺淋巴细胞在生理性免疫老化中的双向调节作用，即功能健全的CD57⁺淋巴细胞有助于维持免疫稳态和健康衰老，而功能失调或过度积累的CD57⁺淋巴细胞则可促进炎症衰老及衰老相关疾病的发生发展。同时，综述了CD57在自身免疫性疾病、恶性肿瘤、代谢性疾病、生殖系统疾病及心血管疾病等多种疾病中的临床相关性及潜在应用价值。最后，本文从分子机制解析、单细胞多组学研究、空间免疫微环境分析及临床转化研究等方面对CD57未来研究方向进行了展望，以期为CD57相关基础研究及临床应用提供理论参考。

Abstract: CD57 is one of the earliest identified surface markers of human natural killer (NK) cells and has long been considered an important phenotypic marker of lymphocyte terminal differentiation and immunosenescence. In recent years, with the development of single-cell sequencing, multiparameter flow cytometry, and spatial transcriptomics technologies, the biological significance of CD57 has been re-evaluated. Its role has expanded from a simple marker of immunosenescence to an important molecule involved in lymphocyte differentiation, functional regulation, and immune homeostasis. This review systematically summarizes the molecular structure and biological characteristics of CD57, with a particular focus on its differential expression patterns and functional features in lymphocyte subsets, including NK cells, T cells, and NKT-like cells. Furthermore, we discuss the functional heterogeneity of CD57⁺ lymphocytes in different immune microenvironments and the potential molecular mechanisms underlying their functional regulation. We also summarize the bidirectional regulatory role of CD57⁺ lymphocytes in physiological immunosenescence, in which functionally competent CD57⁺ lymphocytes contribute to immune homeostasis and healthy aging, whereas dysfunctional or excessively accumulated CD57⁺ lymphocytes may promote inflammaging and age-related diseases. In addition, the clinical relevance and potential applications of CD57 in various diseases, including autoimmune diseases, malignancies, metabolic diseases, reproductive system disorders, and cardiovascular diseases, are reviewed. Finally, future research directions are proposed from the perspectives of molecular mechanism studies, single-cell multi-omics, spatial immune microenvironment analysis, and clinical translational research, in order to provide theoretical insights for basic research and clinical applications related to CD57.