Siglec1-KO Mouse

Siglec1, also known as CD169 or Sialoadhesin (Sn), is a surface adhesion molecule on human myeloid cells and part of the Siglec family. It acts as a receptor for sialylated molecular structures, equipping myeloid cells with functions that reach beyond pathogen elimination. Siglec1 seems to crosslink innate and adaptive immunity by antigen presentation and pathogen elimination, playing a substantial role in immunoregulation [1].

Siglec1 has been studied in various disease contexts. In chronic obstructive pulmonary disease (COPD), Siglec1 overexpression in rat lungs enhanced the expression of inflammatory cytokines in a macrophage cell line. It did so through increasing miR-1260, which degraded IκBα, a key inhibitor in the NF-κB pathway [2]. In melanoma, Siglec1-expressing subcapsular sinus macrophages provided anchorage to pioneer metastatic cells, and the interaction between these macrophages and hypersialylated cancer cells drove cancer cell proliferation [4]. In idiopathic inflammatory myopathies (IIM), SIGLEC1 expression on monocytes could distinguish between active and inactive disease, and was useful for monitoring disease activity and treatment response in juvenile and adult dermatomyositis [3]. In multiple sclerosis (MS), SIGLEC1+ myeloid cells were abundant in active MS lesions, but not in chronic ones, suggesting it could be used to investigate the activity of inflammatory CNS lesions [5]. In systemic lupus erythematosus (SLE), SIGLEC1 was significantly higher in confirmed SLE patients compared to non-SLE patients, with high sensitivity and negative predictive value, making it useful to exclude SLE in suspected cases [6]. In childhood SLE, SIGLEC1 expression on monocytes correlated with disease activity, being a sensitive biomarker for disease monitoring [7]. In Graves' disease, SIGLEC1 expression was upregulated in untreated patients and correlated with thyroid parameters, and inhibiting its expression could reduce proinflammatory cytokine expression in monocytes [8].

In conclusion, Siglec1 plays a crucial role in immunoregulation and is involved in multiple disease processes. Studies in various disease models, including those related to inflammation, cancer metastasis, and autoimmune diseases, have revealed its significance in disease development and progression. Understanding Siglec1 function provides insights into the underlying mechanisms of these diseases, potentially leading to new diagnostic and therapeutic strategies.

References:

1. Herzog, Silva, Fragkou, Paraskevi C, Arneth, Borros M, Mkhlof, Samr, Skevaki, Chrysanthi. 2022. Myeloid CD169/Siglec1: An immunoregulatory biomarker in viral disease. In Frontiers in medicine, 9, 979373. doi:10.3389/fmed.2022.979373. https://pubmed.ncbi.nlm.nih.gov/36213653/

2. Li, Sensen, Jiang, Longfeng, Yang, Yanbing, Deng, Xiaozhao, Li, Yaojun. 2020. Siglec1 enhances inflammation through miR-1260-dependent degradation of IκBα in COPD. In Experimental and molecular pathology, 113, 104398. doi:10.1016/j.yexmp.2020.104398. https://pubmed.ncbi.nlm.nih.gov/32007531/

3. Graf, Manuel, von Stuckrad, Sae Lim, Uruha, Akinori, Schneider, Udo, Rose, Thomas. . SIGLEC1 enables straightforward assessment of type I interferon activity in idiopathic inflammatory myopathies. In RMD open, 8, . doi:10.1136/rmdopen-2021-001934. https://pubmed.ncbi.nlm.nih.gov/35177553/

4. Singh, Rohit, Choi, Beom K. 2019. Siglec1-expressing subcapsular sinus macrophages provide soil for melanoma lymph node metastasis. In eLife, 8, . doi:10.7554/eLife.48916. https://pubmed.ncbi.nlm.nih.gov/31872800/

5. Ostendorf, Lennard, Dittert, Philipp, Biesen, Robert, Paul, Friedemann, Radbruch, Helena. 2021. SIGLEC1 (CD169): a marker of active neuroinflammation in the brain but not in the blood of multiple sclerosis patients. In Scientific reports, 11, 10299. doi:10.1038/s41598-021-89786-0. https://pubmed.ncbi.nlm.nih.gov/33986412/

6. Zorn-Pauly, Lydia, von Stuckrad, Anne Sae Lim, Klotsche, Jens, Alexander, Tobias, Biesen, Robert. . Evaluation of SIGLEC1 in the diagnosis of suspected systemic lupus erythematosus. In Rheumatology (Oxford, England), 61, 3396-3400. doi:10.1093/rheumatology/keab875. https://pubmed.ncbi.nlm.nih.gov/34849605/

7. Stuckrad, Sae Lim von, Klotsche, Jens, Biesen, Robert, Unterwalder, Nadine, Kallinich, Tilmann. 2020. SIGLEC1 (CD169) is a sensitive biomarker for the deterioration of the clinical course in childhood systemic lupus erythematosus. In Lupus, 29, 1914-1925. doi:10.1177/0961203320965699. https://pubmed.ncbi.nlm.nih.gov/33081587/

8. Wang, Yanqiu, Jin, Zhou, Sun, Jiajun, Zhou, Yulin, Wang, Shu. 2022. The role of activated monocyte IFN/SIGLEC1 signalling in Graves' disease. In The Journal of endocrinology, 255, 1-9. doi:10.1530/JOE-21-0453. https://pubmed.ncbi.nlm.nih.gov/35695299/