<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SIGLEC10 — Sialic Acid Binding Ig-Like Lectin 10</th>
</tr>
<tr>
<td class="label">Feature</td>
<td>Value</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>SIGLEC10</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19q13.4</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>89792</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9H7M1</td>
</tr>
<tr>
<td class="label">Genomic Coordinates</td>
<td>chr19:50,884,231-50,901,213 (GRCh38)</td>
</tr>
<tr>
<td class="label">Exon Count</td>
<td>12</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>553 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~60 kDa</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>B cells, monocytes, eosinophils, dendritic cells</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/glioma" style="color:#ef9a9a">Glioma</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">8 edges</a></td>
</tr>
</table>
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SIGLEC10 — Sialic Acid Binding Ig-Like Lectin 10</th>
</tr>
<tr>
<td class="label">Feature</td>
<td>Value</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>SIGLEC10</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19q13.4</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>89792</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9H7M1</td>
</tr>
<tr>
<td class="label">Genomic Coordinates</td>
<td>chr19:50,884,231-50,901,213 (GRCh38)</td>
</tr>
<tr>
<td class="label">Exon Count</td>
<td>12</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>553 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~60 kDa</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>B cells, monocytes, eosinophils, dendritic cells</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/glioma" style="color:#ef9a9a">Glioma</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">8 edges</a></td>
</tr>
</table>
SIGLEC10 (Sialic Acid Binding Ig-Like Lectin 10) is a member of the Siglec family of cell surface lectins that recognize sialic acid residues on glycoconjugates. It is encoded by the SIGLEC10 gene located on chromosome 19q13.4 and is primarily expressed on immune cells including B lymphocytes, monocytes, and eosinophils [1][2]. SIGLEC10 functions as an inhibitory receptor that modulates immune cell activation and plays important roles in immune homeostasis, inflammation, and potentially in neuroimmune interactions relevant to neurodegenerative diseases. [@crocker2020]
The Siglec family consists of at least 14 members in humans, divided into two groups: CD33-related SIGLECs (SIGLEC3, 5, 6, 7, 8, 9, 10, 11, 14, 16) and a conserved subgroup (SIGLEC1, 2, 4) [3]. SIGLEC10 belongs to the CD33-related group and shares structural and functional similarities with SIGLEC9. [@yamaji2022]
SIGLEC10 possesses the characteristic Siglec domain architecture:
SIGLEC10 preferentially binds to:
SIGLEC10 functions primarily as an inhibitory immune receptor through its cytoplasmic ITIM motifs:
SIGLEC10 modulates various immune cell functions:
B Cell Regulation:
A notable interaction is between SIGLEC10 and CD24 (also known as heat-stable antigen or nectin-1), a glycosylphosphatidylinositol (GPI)-anchored protein. The SIGLEC10-CD24 complex provides an inhibitory signal that suppresses inflammatory responses and may be relevant to inflammatory diseases [4].
SIGLEC10 may play a role in Alzheimer's disease through modulation of neuroinflammation:
Microglial Activation:
SIGLEC10 involvement in Parkinson's disease includes:
Microglial Regulation:
SIGLEC10 has been implicated in multiple sclerosis:
Autoimmune Regulation:
Several single nucleotide polymorphisms (SNPs) in SIGLEC10 have been studied:
Genetic studies have linked SIGLEC10 variants to:
SIGLEC10 represents a potential therapeutic target:
Agonists:
SIGLEC10 expression levels may serve as:
SIGLEC10 interacts with several proteins:
SIGLEC10 is an inhibitory sialic acid-binding lectin expressed primarily on immune cells that plays important roles in immune regulation and inflammation. Its expression on microglia and capacity to modulate neuroinflammation make it relevant to neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. Through its ITIM-mediated inhibitory signaling, SIGLEC10 helps maintain immune homeostasis, and alterations in its function may contribute to chronic neuroinflammation and neuronal damage. Understanding SIGLEC10 biology may provide insights into disease mechanisms and therapeutic targets for neurodegenerative disorders.
The interaction between CD24 and SIGLEC10 represents a critical immune regulatory pathway with significant implications for neuroinflammation. CD24 (also known as heat-stable antigen or nectin-1) is a heavily glycosylated GPI-anchored protein expressed on many cell types including neurons, immune cells, and various tissues. The CD24-SIGLEC10 interaction provides a dual inhibitory signal that suppresses inflammatory responses through a mechanism distinct from other immune checkpoints. Upon CD24 engagement, SIGLEC10 becomes activated and recruits SHP-1 to its ITIM motifs, leading to downstream suppression of NF-κB and other pro-inflammatory signaling pathways. This axis is particularly important in the brain where CD24 is expressed on neurons and may help protect against excessive microglial activation. Dysregulation of the CD24-SIGLEC10 axis has been implicated in chronic neuroinflammation and may contribute to neurodegenerative disease progression [@chen2024].
SIGLEC10 plays a major role in regulating B cell receptor (BCR) signaling, which is central to antibody-mediated immunity and autoimmunity. When SIGLEC10 is engaged alongside the BCR, its ITIMs become phosphorylated and recruit SHP-1, which then dephosphorylates key signaling molecules in the BCR activation cascade. This results in reduced B cell activation, antibody production, and potentially altered B cell development. The regulation of B cell function by SIGLEC10 has implications for both protective immunity and autoimmune disease. In the context of neurodegeneration, B cells and their antibodies may contribute to neuroinflammation through multiple mechanisms including direct recognition of neuronal antigens, cytokine production, and interaction with other immune cells. Understanding how SIGLEC10 modulates B cell responses may provide insights into autoimmune components of neurodegenerative diseases [@taylor2023].
SIGLEC10 is highly expressed on eosinophils, where it plays a crucial role in regulating allergic inflammation and immune responses to parasitic infections. Eosinophil activation leads to degranulation and release of cytotoxic granule proteins that can cause tissue damage. SIGLEC10 engagement suppresses these effector functions, providing a brake on eosinophil-mediated inflammation. The relevance of eosinophil regulation to neurodegeneration is increasingly recognized, as eosinophils can infiltrate the CNS in certain neurological conditions and contribute to neuroinflammatory processes. Additionally, the link between peripheral allergic inflammation and CNS disease suggests that SIGLEC10-mediated eosinophil regulation may have broader implications for neuroimmune interactions.
SIGLEC10 has been implicated in rheumatoid arthritis (RA), a chronic autoimmune disease characterized by joint inflammation and destruction. Studies have identified polymorphisms in the SIGLEC10 gene that are associated with altered RA susceptibility, suggesting that genetic variations in this inhibitory receptor may influence disease risk. The function of SIGLEC10 in RA likely involves regulation of inflammatory responses in the joints, potentially through modulation of synovial macrophages and other immune cells. The balance between activating and inhibitory Siglecs in the joint may determine the magnitude of inflammatory responses and the extent of tissue damage. Therapeutic modulation of SIGLEC10 function could represent a novel approach to treating RA and other autoimmune conditions [@murphy2022].
In systemic lupus erythematosus (SLE), SIGLEC10 may contribute to the dysregulated immune responses characteristic of this autoimmune disease. Altered expression of SIGLEC10 on B cells and other immune cells has been reported in SLE patients, potentially reflecting disease-related immune activation or genetic influences on SIGLEC10 regulation. Given the role of SIGLEC10 in B cell regulation, changes in its expression or function could contribute to the autoantibody production that is a hallmark of SLE. The sialylated self-antigens that accumulate in SLE may also engage SIGLEC10 in ways that alter immune tolerance. Further research into SIGLEC10 in SLE may reveal novel biomarkers or therapeutic targets for this complex autoimmune disease.
SIGLEC10 may influence amyloid-β clearance in Alzheimer's disease through modulation of microglial phagocytosis. Microglia express multiple receptors that recognize amyloid plaques, and the net effect of these receptor interactions determines whether plaques are efficiently cleared or accumulate over time. SIGLEC10 engagement with sialylated molecules on amyloid deposits may provide inhibitory signals that modulate the efficiency of microglial clearance. The sialylation state of amyloid plaques may change during disease progression, altering SIGLEC10 engagement and clearance efficiency. Genetic variants that affect SIGLEC10 function could therefore modify an individual's risk of developing AD by altering amyloid clearance capacity [@yang2023].
SIGLEC10 may influence tau pathology through its effects on neuroinflammation. Tau phosphorylation and spread are driven by inflammatory processes in the brain, and SIGLEC10's anti-inflammatory function may help limit these processes. Under normal conditions, SIGLEC10 on microglia would suppress excessive inflammatory responses that could promote tau pathology. In disease states, dysregulation of SIGLEC10 could lead to unchecked neuroinflammation that accelerates tau phosphorylation and propagation. The genetic associations between SIGLEC variants and AD risk support a role for this immune regulatory pathway in disease pathogenesis. Understanding the precise mechanisms by which SIGLEC10 influences tau pathology may reveal novel therapeutic targets.
SIGLEC10 is expressed on brain endothelial cells where it may regulate immune cell trafficking across the blood-brain barrier (BBB). The BBB is a critical interface that controls the entry of immune cells and molecules into the CNS, and its dysfunction is a feature of many neurodegenerative diseases. SIGLEC10 on endothelial cells may help maintain BBB integrity by suppressing inflammatory responses that would otherwise compromise barrier function. Additionally, SIGLEC10 may regulate the adhesion and transmigration of immune cells across the BBB, controlling the influx of peripheral immune cells that can contribute to neuroinflammation. Therapeutic strategies that enhance SIGLEC10 function could potentially help restore BBB integrity in neurodegenerative diseases.
Synthetic SIGLEC10 agonists represent a promising therapeutic approach for neuroinflammatory conditions. These agonists could engage SIGLEC10 and activate its inhibitory signaling pathways, suppressing excessive immune responses that drive neurodegeneration. Antibody-based agonists that cluster SIGLEC10 on the cell surface are particularly effective at activating ITIM signaling. Sialylated ligand mimetics provide another approach to SIGLEC10 activation, though careful design is needed to avoid potential exploitation by pathogens. The challenge in developing SIGLEC10 agonists lies in achieving sufficient specificity and avoiding off-target effects on other Siglec family members. Preclinical models suggest that SIGLEC10 agonists could be effective in treating chronic neuroinflammatory conditions, though clinical development is still in early stages [@patel2024].
While SIGLEC10 agonists would be useful for treating neuroinflammation, SIGLEC10 antagonists may have a role in cancer immunotherapy. Blocking SIGLEC10 could enhance anti-tumor immune responses by removing an inhibitory checkpoint on immune cells. This approach would be particularly relevant for tumors that express high levels of sialylated ligands that engage SIGLEC10. The development of SIGLEC10-blocking antibodies and small molecule antagonists is an active area of research in immuno-oncology. Combination approaches that block multiple immune checkpoints may provide synergistic anti-tumor effects. The identification of patients whose tumors are likely to respond to SIGLEC10 blockade will be important for clinical development.
Gene therapy approaches to enhance SIGLEC10 expression represent a novel strategy for treating neuroinflammatory diseases. Viral vector delivery of SIGLEC10 to the brain could increase inhibitory signaling in microglia, suppressing chronic neuroinflammation. This approach would be particularly relevant for diseases where SIGLEC10 expression is downregulated or where enhanced inhibitory signaling would be beneficial. AAV vectors have shown promise for delivering genes to the CNS and could be adapted for SIGLEC10 delivery. Challenges include achieving appropriate expression levels, avoiding off-target effects, and ensuring long-term expression. Gene therapy approaches for neurodegenerative diseases are in active development, and SIGLEC10 enhancement may become a viable strategy in the future.
Interactive diagram showing SIGLEC10's key relationships in the SciDEX knowledge graph (8 connections shown).
The following diagram shows the key molecular relationships involving SIGLEC10 — Sialic Acid Binding Ig-Like Lectin 10 discovered through SciDEX knowledge graph analysis: