Siglece-KO Mouse

Siglec-E, also known as sialic acid-binding immunoglobulin-like lectin E, is an important immune-regulatory receptor. It belongs to the Siglec family and binds to sialic acid-containing glycans. Siglec-E is involved in immune-related pathways, regulating immune cell activation and immune responses, which is of great biological significance in maintaining immune homeostasis [2,3,4,5,6,7,8]. Gene knockout mouse models have been crucial for studying its functions.

In glioblastoma, deletion of Siglec-E (murine homolog of Siglec-9) led to restrained tumor development and prolonged survival. It directly activated CD4+ and CD8+ T cells through antigen presentation, chemokine secretion, and co-stimulatory factor interactions, and synergized with anti-PD-1/PD-L1 treatment to enhance antitumor efficacy [1]. In multiple murine cancer models, Siglec-E knockout in myeloid cells prolonged survival and increased tumor infiltration of activated T cells, indicating its role in modulating anticancer immunity [8]. In meta-inflammation and metabolic disorder, inactivation of the CD24-Siglec-E pathway exacerbated diet-induced metabolic disorders, while CD24Fc treatment alleviated them, suggesting its role in suppressing obesity-related metabolic dysfunction [5].

In conclusion, Siglec-E plays a significant role in immune regulation and is involved in various disease conditions such as cancer and metabolic disorders. Studies using Siglec-E knockout mouse models have revealed its functions in tumor growth regulation, immune cell activation, and metabolic disease modulation, providing valuable insights for potential therapeutic strategies in these disease areas.

References:

1. Mei, Yan, Wang, Xiumei, Zhang, Ji, Chen, Jun, Jia, Guangshuai. 2023. Siglec-9 acts as an immune-checkpoint molecule on macrophages in glioblastoma, restricting T-cell priming and immunotherapy response. In Nature cancer, 4, 1273-1291. doi:10.1038/s43018-023-00598-9. https://pubmed.ncbi.nlm.nih.gov/37460871/

2. Stanczak, Michal A, Rodrigues Mantuano, Natalia, Kirchhammer, Nicole, Zippelius, Alfred, Läubli, Heinz. 2022. Targeting cancer glycosylation repolarizes tumor-associated macrophages allowing effective immune checkpoint blockade. In Science translational medicine, 14, eabj1270. doi:10.1126/scitranslmed.abj1270. https://pubmed.ncbi.nlm.nih.gov/36322632/

3. Gray, Melissa A, Stanczak, Michal A, Mantuano, Natália R, Läubli, Heinz, Bertozzi, Carolyn R. 2020. Targeted glycan degradation potentiates the anticancer immune response in vivo. In Nature chemical biology, 16, 1376-1384. doi:10.1038/s41589-020-0622-x. https://pubmed.ncbi.nlm.nih.gov/32807964/

4. Smith, Benjamin A H, Deutzmann, Anja, Correa, Kristina M, Felsher, Dean W, Bertozzi, Carolyn R. 2023. MYC-driven synthesis of Siglec ligands is a glycoimmune checkpoint. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2215376120. doi:10.1073/pnas.2215376120. https://pubmed.ncbi.nlm.nih.gov/36897988/

5. Wang, Xu, Liu, Mingyue, Zhang, Jifeng, Zheng, Pan, Liu, Yang. . CD24-Siglec axis is an innate immune checkpoint against metaflammation and metabolic disorder. In Cell metabolism, 34, 1088-1103.e6. doi:10.1016/j.cmet.2022.07.005. https://pubmed.ncbi.nlm.nih.gov/35921817/

6. Schmassmann, Philip, Roux, Julien, Buck, Alicia, Läubli, Heinz, Hutter, Gregor. 2023. Targeting the Siglec-sialic acid axis promotes antitumor immune responses in preclinical models of glioblastoma. In Science translational medicine, 15, eadf5302. doi:10.1126/scitranslmed.adf5302. https://pubmed.ncbi.nlm.nih.gov/37467314/

7. Liao, Chaoxiong, Luo, Shuhua, Liu, Xiaolei, Ma, Daqing, Tang, Jing. 2024. Siglec-F+ neutrophils in the spleen induce immunosuppression following acute infection. In Theranostics, 14, 2589-2604. doi:10.7150/thno.93812. https://pubmed.ncbi.nlm.nih.gov/38646647/

8. Wieboldt, Ronja, Sandholzer, Michael, Carlini, Emanuele, Läubli, Heinz, Mantuano, Natalia Rodrigues. 2024. Engagement of sialylated glycans with Siglec receptors on suppressive myeloid cells inhibits anticancer immunity via CCL2. In Cellular & molecular immunology, 21, 495-509. doi:10.1038/s41423-024-01142-0. https://pubmed.ncbi.nlm.nih.gov/38448555/