Department of Endocrinology and Metabolism, the First Hospital of Jilin University, Changchun 130021, China; Key Laboratory of Organ Regeneration & Transplantation of Ministry of Education, The First Hospital of Jilin University, Changchun 130021, China; National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun 130021, China.
Department of Oncology, the First Hospital of Jilin University, Changchun 130021, China.
Int Immunopharmacol. 2024 May 30;133:112088. doi: 10.1016/j.intimp.2024.112088. Epub 2024 Apr 15.
The signaling lymphocytic activation molecule (SLAM) family participates in the modulation of various innate and adaptive immune responses. SLAM family (SLAMF) receptors include nine transmembrane glycoproteins, of which SLAMF3 (also known as CD229 or Ly9) has important roles in the modulation of immune responses, from the fundamental activation and suppression of immune cells to the regulation of intricate immune networks. SLAMF3 is mainly expressed in immune cells, such as T, B, and natural killer cells. It has a unique molecular structure, including four immunoglobulin-like domains in the extracellular domain and two immunoreceptor tyrosine-based signaling motifs in the intracellular structural domains. These unique structures have important implications for protein functioning. SLAMF3 is involved in pathogenesis of various disease, particularly autoimmune diseases and cancer. However, despite its potential clinical significance, a comprehensive overview of the current paradigm of SLAMF3 research is lacking. This review summarizes the structure, functional mechanisms, and therapeutic implications of SLAMF3. Our findings highlight the significance of SLAMF3 in both physiological and pathological contexts, and underline its dual role in autoimmunity and malignancies, and including disease progression and prognosis. The review also proposes that future studies on SLAMF3 should explore its context-specific inhibitory and stimulatory effects, expand on its potential in disease mapping, investigate related signaling pathways, and explore its value as a drug target. Research in these areas related to SLAMF3 can provide more precise directions for future therapeutic strategies.
信号淋巴细胞激活分子 (SLAM) 家族参与调节各种先天和适应性免疫反应。SLAM 家族 (SLAMF) 受体包括九个跨膜糖蛋白，其中 SLAMF3（也称为 CD229 或 Ly9）在调节免疫反应方面具有重要作用，从免疫细胞的基本激活和抑制到复杂免疫网络的调节。SLAMF3 主要在免疫细胞（如 T、B 和自然杀伤细胞）中表达。它具有独特的分子结构，包括细胞外结构域中的四个免疫球蛋白样结构域和细胞内结构域中的两个免疫受体酪氨酸基信号基序。这些独特的结构对蛋白质功能具有重要意义。SLAMF3 参与各种疾病的发病机制，特别是自身免疫性疾病和癌症。然而，尽管它具有潜在的临床意义，但对 SLAMF3 研究的当前范例缺乏全面的概述。本综述总结了 SLAMF3 的结构、功能机制和治疗意义。我们的研究结果强调了 SLAMF3 在生理和病理环境中的重要性，并强调了它在自身免疫和恶性肿瘤中的双重作用，包括疾病进展和预后。该综述还提出，未来对 SLAMF3 的研究应探索其特定于上下文的抑制和刺激作用，扩大其在疾病图谱中的潜力，研究相关信号通路，并探索其作为药物靶点的价值。与 SLAMF3 相关的这些领域的研究可以为未来的治疗策略提供更精确的方向。
