Siglecg-KO Mouse

Siglec-G, a sialic acid-binding immunoglobulin-like lectin, is mainly expressed in hematopoietic cells. It functions as an inhibitory receptor, often binding to sialic acid-containing ligands like CD24. This interaction is part of the CD24-Siglec-G pathway which represses tissue damage-induced immune responses, discriminates between danger-and pathogen-associated molecular patterns, and plays a role in maintaining immune cell homeostasis [1,6].

In gene-knockout (KO) mouse models, Siglec-G deficiency led to the expansion of B1a B cell lineages, likely by enhancing NFκB activation [2]. In the context of systemic lupus erythematosus (SLE), double-deficient mice (Siglec-G -/- x Dnase1 -/- or Siglec-G -/- x Dnase1l3 -/-) showed more severe disease manifestations compared to single-deficient mice, highlighting epistatic effects [3]. Also, in sepsis models, neutrophil-mediated cleavage of Siglec-G disrupted B-1a cell homeostasis, while a decoy peptide protecting Siglec-G improved sepsis outcomes [4]. Moreover, ablation of Siglec-G enhanced the efficacy of adoptively transferred T cells and chimeric antigen receptor (CAR) T cells in suppressing solid tumors, as Siglec-G was found to limit CD8+ T cell function through metabolic rewiring [5].

In conclusion, Siglec-G plays a crucial role in regulating immune cell homeostasis and immune responses. Studies using KO mouse models have revealed its significance in diseases such as SLE, sepsis, and cancer. Understanding Siglec-G's function can potentially provide new therapeutic strategies for these diseases.

References:

1. Chen, Guo-Yun, Tang, Jie, Zheng, Pan, Liu, Yang. 2009. CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. In Science (New York, N.Y.), 323, 1722-5. doi:10.1126/science.1168988. https://pubmed.ncbi.nlm.nih.gov/19264983/

2. Ding, Cheng, Liu, Yan, Wang, Yin, Zheng, Pan, Liu, Yang. 2007. Siglecg limits the size of B1a B cell lineage by down-regulating NFkappaB activation. In PloS one, 2, e997. doi:. https://pubmed.ncbi.nlm.nih.gov/17912374/

3. Korn, Marina A, Steffensen, Marie, Brandl, Carolin, Winkler, Thomas H, Nitschke, Lars. 2023. Epistatic effects of Siglec-G and DNase1 or DNase1l3 deficiencies in the development of systemic lupus erythematosus. In Frontiers in immunology, 14, 1095830. doi:10.3389/fimmu.2023.1095830. https://pubmed.ncbi.nlm.nih.gov/36969253/

4. Tan, Chuyi, Reilly, Bridgette, Ma, Gaifeng, Aziz, Monowar, Wang, Ping. 2024. Neutrophils disrupt B-1a cell homeostasis by targeting Siglec-G to exacerbate sepsis. In Cellular & molecular immunology, 21, 707-722. doi:10.1038/s41423-024-01165-7. https://pubmed.ncbi.nlm.nih.gov/38789529/

5. Yin, Shenhui, Li, Chunzhen, Shen, Xin, Yu, Yizhi, Xu, Sheng. 2024. Siglec-G Suppresses CD8+ T Cells Responses through Metabolic Rewiring and Can be Targeted to Enhance Tumor Immunotherapy. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2403438. doi:10.1002/advs.202403438. https://pubmed.ncbi.nlm.nih.gov/39373395/

6. Chen, Guo-Yun, Chen, Xi, King, Samantha, Zheng, Pan, Liu, Yang. 2011. Amelioration of sepsis by inhibiting sialidase-mediated disruption of the CD24-SiglecG interaction. In Nature biotechnology, 29, 428-35. doi:10.1038/nbt.1846. https://pubmed.ncbi.nlm.nih.gov/21478876/