Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan, China; Department of Clinical Laboratory, Children's Hospital and Women Health Center of Shanxi, Taiyuan, China.
Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan, China; Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Taiyuan, China.
Prog Biophys Mol Biol. 2023 Jan;177:34-41. doi: 10.1016/j.pbiomolbio.2022.10.006. Epub 2022 Oct 18.
Siglec-15 is a highly conserved member of the Siglec family, expressed on osteoclasts, a subset of myeloid cells and some cancer cells. Except for regulating osteoclast differentiation, Siglec-15 engages in immunoregulation as an immune suppressor. Siglec-15 functions as an immunosuppressive molecule in tumor-associated macrophage-mediated T cell immunity in the tumor microenvironment (TME), which makes Siglec-15 to be an emerging and promising target for normalization cancer immunotherapy. Besides, Siglec-15 interacts with sialylated pathogens and modulates host immune response against microbial pathogens by altering cytokine production and/or phagocytosis, which further broadens the underlying pathophysiological roles of Siglec-15. The fact that N-glycosylation and sialylation of Siglec-15 play a pivotal role in Siglec-15 biological function indicates that targeting certain post-translational modification may be an effective strategy for targeting Siglec-15 therapy. In-depth exploring Siglec-15 biology function is crucial for better design of Siglec-15-based therapy according to different clinical indications.
Siglec-15 是 Siglec 家族中高度保守的成员，表达于破骨细胞、髓系细胞的一个子集和一些癌细胞上。除了调节破骨细胞分化外，Siglec-15 还作为免疫抑制因子参与免疫调节。Siglec-15 在肿瘤微环境（TME）中肿瘤相关巨噬细胞介导的 T 细胞免疫中作为一种免疫抑制分子发挥作用，这使得 Siglec-15 成为癌症免疫治疗规范化的一个新兴且有前途的靶点。此外，Siglec-15 与唾液酸化病原体相互作用，并通过改变细胞因子产生和/或吞噬作用来调节宿主对微生物病原体的免疫反应，这进一步扩大了 Siglec-15 的潜在病理生理作用。Siglec-15 的 N-糖基化和唾液酸化在 Siglec-15 生物学功能中起着关键作用，这表明针对某些翻译后修饰可能是针对 Siglec-15 治疗的有效策略。深入探索 Siglec-15 的生物学功能对于根据不同的临床适应症更好地设计基于 Siglec-15 的治疗方法至关重要。
