This website uses cookies to ensure you get the best experience on our website.
- Table of Contents
Facts about Sialic acid-binding Ig-like lectin 15.
Human | |
---|---|
Gene Name: | SIGLEC15 |
Uniprot: | Q6ZMC9 |
Entrez: | 284266 |
Belongs to: |
---|
immunoglobulin superfamily |
CD33 antigen-like 3SIGLEC-15; CD33 molecule-like 3; CD33L3; HsT1361; sialic acid binding Ig-like lectin 15; sialic acid-binding Ig-like lectin 15; Siglec15; Siglec-15
Mass (kDA):
35.653 kDA
Human | |
---|---|
Location: | 18q12.3 |
Sequence: | 18; NC_000018.10 (45825675..45844094) |
Expressed in macrophage and/or dendritic cells of spleen and lymph nodes.
Membrane; Single-pass type I membrane protein.
The SIGLEC15 Gene is a key regulator for several immune cell functions. This includes the killing of immune cells, production cytokines, as well as pathogen clearance. This article discusses the regulatory roles of the SIGLEC15 protein in human cells. Continue reading for more information. We'll talk about the most common uses of SIGLEC15 in human cells.
Hiruma, along with his colleagues, first identified the Siglec15 genetic mutation. They showed that this gene was expressed on a type of bone tumor called giant cell tumor. The cells of this type resemble osteoclasts. To suppress osteoclast differentiation, the investigators used a monoclonal antibody against Siglec15 in RAW264.7 bone marrow macrophage and mouse macrophage cell lines.
RNA-Seq tests were used on OS cells to determine the differentially expressed genes. They discovered that Siglec-15 expression promoted cell proliferation and colony-formation. RNA-Seq analysis of both groups showed that siglec-15 gene expression is strongly correlated to the presence of THCA. The SIGLEC15 genes may play an essential role in diagnosing THCA.
Siglec15 was found to be upregulated in many types of human cancers. This may have some clinical significance. The gene was detected in tumor cells as well tumor-associated myeloid and CD68+ myeloid tissues. However, the gene was not found to be significantly related to the anti-tumor marker PD–L1. Only 3% of patients actually had both genes.
It is possible that Siglec-15 plays a role in activation of DUSP1, a tumor suppressor. It also negatively regulates MAPK activities. Siglec-15 knockdown decreased DUSP1 transcription and promoted activation JNK/MAPK/MAPK, p38/MAPKK, and P38/MAPK. Additionally, siglec15 gene knockdown resulted in the inhibition of expression of several EMT markers.
Several studies have shown that the expression of Siglec15 correlates with the number of other BLCA-related genes. These genes have been identified by the Drugbank database. It is possible to reduce the incidences of BLCA by using anti-Siglec15 inhibitions. It is possible, through the reduction of SIGLEC15, to develop new strategies for treating various types of cancers.
Siglec15 can be expressed in many TME markers, but it is only for TME. Anti-Siglec15 immunotherapy is less likely to cause side effects if Siglec15 has been targeted in TME. Siglec15 has an immunosuppressive effect that is most apparent in BLCA. This makes it an ideal candidate to be treated with anti-Siglec15 vaccines.
The Siglec protein was found in the genomes of many murine and human cancers. Its function as an immune control point was examined. Glycans in the tumor microenvironment functioned as ligands to Siglecs, which then modulated their expression. In this study, we showed that siglec-E deficiency led to a stronger inflammatory response.
A human siglec-9 human transgenic mouse was used for Siglec-9 to express Siglec-9 a protein that binds specifically to Siglecs from murine tumor cells. Siglec E-transgenic mice had higher CD8+ cell production and were crossbred to Siglec-9-expressing mice. Mice expressing siglec-9 showed increased tumor growth and larger tumors.
In pan-cancer studies, Siglec15 correlated with 122 immunomodulators and four immune checkpoints, including PD-L1 and CTLA-4. Siglec15 is also associated with 28 immune cell types within the tumor. Correlation coefficients were calculated with the ssGSEA algorithm and are presented below. Statistical significance was indicated by asterisks in the table.
One study found that human primary NSCLC-cells expressed higher levels SIGLEC-9 antibody in one than GNEKO or CD25+ cells. Comparing healthy donors, the results were similar. The siglec-9 expression in the other study was lower than it was in healthy donors. In a separate study, we used polyclonally activated peripheral CD8+ T cells. In this study, the age of the participants was not considered.
The role of Siglecs in regulating leukocyte functions is not well understood. Although they have many roles, it is difficult to define them. To pinpoint specific ligands, a combination of biochemical analyses and genetically modified mice is necessary. We can uncover the intricate factors involved by dissecting signalling pathways. This research is crucial in determining the precise functions of immune cells.
These results suggest that Siglec15 gene methylation can reduce its expression. The gene can also have its expression reduced by methylation. So, we may be able identify alternative therapeutic strategies for anti-Siglec15 inhibitors. We also suggest siglec15 epigenetic modification as an alternative to antiSiglec15 inhibits.
This project aims create polyclonal anti-Staphylococcusaureus proteinA antibodies for use in bacteriological testing of milk. The project also created an immunization product that can detect the presence of responders. Scientists are expected to use the findings of this project to develop new techniques for ex vivo expansion.
Siglecs are also promising in treating sepsis. It has a multifactorial mechanism of action, while blunt tools have not been effective. Siglec G, for example in a mouse model sepsis, prevents the development or inflammation in the gut and protects neutrophils from acute pulmonary inflammation. Nanoparticles coated with a 2,8–linked dialic acid worked as an Siglec agonist.
Studies have also suggested that siglecs might be involved in immune cell death and pathogen clearance. Their presence is linked with a variety inflammation phenotypes such as cancer, infectious disorders, and neuroscience. The precise role of Siglecs' remains a mystery. It is currently unclear whether Siglec-15 ligands inhibit tumour growth or T cell infiltration.
Siglecs can be used as immunotherapy targets for cancer. They are related to the B7 family of regulatory immune receptors and exhibit similar molecular structures. However, it is not known what Siglecs do to macrophages. However, the SNP corresponding to this gene correlates strongly with higher survival rates in non-small cells lung cancer patients.
This marker is widely used for clinical trials and research in order to evaluate the efficacy of cytokine production. It is particularly useful in identifying inflammatory conditions in patients, such as cancers. Researchers also hope to use it in immunotherapy trials. It is also useful in clinical trials and can be used for the discovery of new drugs. This research will prove invaluable to the research community.
The SIGLEC15 Gene is involved with antigen-specific T cells responses. Siglec-15 can be suppressed in cells that lack it. The immune system responds to antigens through suppressing the production T-cells. However, this suppressive function isn't limited to T-cells. It can also cause the contraction of T cell. SIGLEC15 suppressive activity is independent of B7-h2/PD-1 axis. This suggests that the two work in different ways.
Siglec-15, which is unlike other T cell receptors, has a sialyl-dependent function and may also regulate specific immune responses to cells. It recognizes a variety glycans and Sialyl Tn-containing molecules. These molecules are associated with specific cell types. Boster Bio's SIGLEC15 gene profil also provides insight into Siglec-15 role in immunity and pathogen clearance.
The gene is highly expressed in all types of human cancers. While Siglec-15 expression is most prevalent in colon, endometrial, thyroid, and bladder cancer, it is also upregulated in kidney and bladder cancer. Siglec-15 is associated with CD3E/IFNG, GZMA/GZMB and CD3E in human bladder cancer. The gene may be useful in disease-fighting activities even if it is not mutated by pathogens.
To measure the level of SIGLEC15 in peripheral blood cells, human CD14+ monocytes were incubated in the presence of 100 ng/ml M-CSF + IFN-g for 7 days. Siglec-15 mRNA levels were determined by RTPCR after seven days. Intra-sample normalization was done to GAPDH. The results were analysed using flow cytometry.
This study found that SIGLEC15 is upregulated selectively in human cancer cells and infiltrating macrophages and myeloid cells. This suppression appears to be dependent on IL-10 which can be produced both by myeloid and T cells. The gene is also rarely expressed in tumor-associated cells or mouse tumors. The authors report that siglec-15 expression doesn't affect B7-h2 expression.
In addition to osteoporosis, a number of other diseases are associated with Siglec-15. Recent studies have shown Siglec-15 could be used as a therapeutic target in osteoporosis. Takahata (and colleagues) have also reported that siglec-15 suppresses osteoclast differentiate in antigen induced arthritis mice, which is a model of Rheumatoid Arthritis.
PMID: 17483134 by Angata T., et al. Siglec-15: an immune system Siglec conserved throughout vertebrate evolution.