Siglec1-KO Mouse

Siglec1, also known as CD169 or Sialoadhesin (Sn), is a cell surface adhesion molecule on human myeloid cells and a member of the Siglec family. It acts as a receptor for sialylated molecular structures, equipping myeloid cells with functions extending beyond pathogen elimination. Siglec1 seems to bridge innate and adaptive immunity through antigen presentation and pathogen elimination, being a significant part of immunoregulation [1].

Siglec1 has been associated with multiple diseases. In COPD, its overexpression in rat lungs enhances inflammation via miR-1260-dependent degradation of IκBα [2]. In melanoma, Siglec1-expressing subcapsular sinus macrophages interact with pioneer metastatic cells, driving cell cycle progression and metastatic colonization [3]. In idiopathic inflammatory myopathies, SIGLEC1 can assess type I interferon activity and monitor disease activity and treatment response in juvenile and adult dermatomyositis [4]. In multiple sclerosis, SIGLEC1+ myeloid cells are present in active brain lesions, potentially indicating inflammatory CNS lesion activity [5]. In systemic lupus erythematosus, SIGLEC1 shows high diagnostic accuracy, and in childhood SLE, its expression on monocytes is a sensitive biomarker for disease activity [6,8]. In Graves' disease, type I IFN-induced SIGLEC1 expression in monocytes is upregulated, correlating with thyroid parameters [7].

In conclusion, Siglec1 plays crucial roles in immunoregulation and is involved in various disease processes, including inflammation, cancer metastasis, and autoimmune diseases. Research on Siglec1 using in vivo models like KO or CKO mouse models (although not explicitly detailed in these references) could potentially further clarify its exact mechanisms in these diseases, providing insights for diagnosis, treatment, and understanding of immunological functions.

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. 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/

4. 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/

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. 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/

8. 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/