Siglecs as Immune Cell Checkpoints in Disease

2020 ◽  
Vol 38 (1) ◽  
pp. 365-395 ◽  
Author(s):  
Shiteng Duan ◽  
James C. Paulson
Keyword(s):  
Immune System ◽  
Sialic Acid ◽  
Cell Signaling ◽  
Blood Cells ◽  
Immune Cell ◽  
White Blood Cells ◽  
Therapeutic Interventions ◽  
Cell Type ◽  
Cell Responses ◽  
Sialic Acid Binding

Sialic acid–binding immunoglobulin-type lectins (Siglecs) are expressed on the majority of white blood cells of the immune system and play critical roles in immune cell signaling. Through recognition of sialic acid–containing glycans as ligands, they help the immune system distinguish between self and nonself. Because of their restricted cell type expression and roles as checkpoints in immune cell responses in human diseases such as cancer, asthma, allergy, neurodegeneration, and autoimmune diseases they have gained attention as targets for therapeutic interventions. In this review we describe the Siglec family, its roles in regulation of immune cell signaling, current efforts to define its roles in disease processes, and approaches to target Siglecs for treatment of human disease.

scholarly journals Terminal Epitope-Dependent Branch Preference of Siglecs Toward N-Glycans

2021 ◽  
Vol 8 ◽  
Author(s):  
Shuaishuai Wang ◽  
Congcong Chen ◽  
Minhui Guan ◽  
Ding Liu ◽  
Xiu-Feng Wan ◽  
...  
Keyword(s):  
Immune System ◽  
Sialic Acid ◽  
Cell Signaling ◽  
Immune Cell ◽  
Glycan Microarray ◽  
New Information ◽  
Sialic Acid Binding ◽  
Complex Glycans ◽  
Complex Glycan

Siglecs are sialic acid–binding immunoglobulin-like lectins that play vital roles in immune cell signaling. Siglecs help the immune system distinguish between self and nonself through the recognition of glycan ligands. While the primary binding specificities of Siglecs are known to be divergent, their specificities for complex glycans remain unclear. Herein, we determined N-glycan binding profiles of a set of Siglecs by using a complex asymmetric N-glycan microarray. Our results showed that Siglecs had unique terminal epitope-dependent branch preference when recognizing asymmetric N-glycans. Specifically, human Siglec-3, -9, and -10 prefer the α1-3 branch when Siaα2-6Galβ1-4GlcNAc terminal epitope serves as the binding ligand but prefer the opposite α1-6 branch when Siaα2-3Galβ1-4GlcNAc epitope serves as the ligand. Interestingly, Siglec-10 exhibited dramatic binding divergence toward a pair of Neu5Ac-containing asymmetric N-glycan isomers, as well as their Neu5Gc-containing counterparts. This new information on complex glycan recognition by Siglecs provides insights into their biological roles and applications.

scholarly journals Hypersialylation in Cancer: Modulation of Inflammation and Therapeutic Opportunities

Cancers ◽  
2018 ◽  
Vol 10 (6) ◽  
pp. 207 ◽  
Author(s):  
Emily Rodrigues ◽  
Matthew Macauley
Keyword(s):  
Sialic Acid ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Immune Cell ◽  
Cell Types ◽  
Functional Roles ◽  
Cell Responses ◽  
Disease Prognosis ◽  
Sialic Acid Binding ◽  
Cancer Types

Cell surface glycosylation is dynamic and often changes in response to cellular differentiation under physiological or pathophysiological conditions. Altered glycosylation on cancers cells is gaining attention due its wide-spread occurrence across a variety of cancer types and recent studies that have documented functional roles for aberrant glycosylation in driving cancer progression at various stages. One change in glycosylation that can correlate with cancer stage and disease prognosis is hypersialylation. Increased levels of sialic acid are pervasive in cancer and a growing body of evidence demonstrates how hypersialylation is advantageous to cancer cells, particularly from the perspective of modulating immune cell responses. Sialic acid-binding receptors, such as Siglecs and Selectins, are well-positioned to be exploited by cancer hypersialylation. Evidence is also mounting that Siglecs modulate key immune cell types in the tumor microenvironment, particularly those responsible for maintaining the appropriate inflammatory environment. From these studies have come new and innovative ways to block the effects of hypersialylation by directly reducing sialic acid on cancer cells or blocking interactions between sialic acid and Siglecs or Selectins. Here we review recent works examining how cancer cells become hypersialylated, how hypersialylation benefits cancer cells and tumors, and proposed therapies to abrogate hypersialylation of cancer.

scholarly journals Association between serum markers of the humoral immune system and inflammation in the Swedish AMORIS study

2020 ◽  
Author(s):  
aida santaolalla ◽  
Sam Sollie ◽  
Ali Rislan ◽  
Debra H. Josephs ◽  
Niklas Hammar ◽  
...  
Keyword(s):  
Immune System ◽  
Educational Level ◽  
Blood Cells ◽  
Adaptive Response ◽  
White Blood Cells ◽  
Principal Component ◽  
Serum Markers ◽  
Response Component ◽  
Humoral Immune ◽  
Humoral Immune System

Abstract Background: Although the onset of inflammatory cascades may profoundly influence the nature of antibody responses, the interplay between inflammatory and humoral (antibody) immune markers remains unclear. Thus, we explored the reciprocity between the humoral immune system and inflammation and assessed how external socio-demographic factors may influence these interactions.Methods: From the AMORIS cohort, 5,513 individuals were identified with baseline measurements of serum humoral immune (immunoglobulin G, A & M (IgG, IgA, IgM)) and inflammation (C-reactive protein (CRP), albumin, haptoglobin, white blood cells (WBC), iron and total iron-binding capacity) markers measured on the same day. Correlation analysis, principal component analysis and hierarchical clustering were used to evaluate biomarkers correlation, variation and associations. Multivariate analysis of variance was used to assess associations between biomarkers and educational level, socio-economic status, sex and age.Results: Frequently used serum markers for inflammation, CRP, haptoglobin and white blood cells, correlated together. Hierarchical clustering and principal component analysis confirmed the interaction between these main biological responses, showing an acute response component (CRP, Haptoglobin, WBC, IgM) and adaptive response component (Albumin, Iron, TIBC, IgA, IgG). A socioeconomic gradient associated with worse health outcomes was observed, specifically low educational level, older age and male sex were associated with serum levels that indicated infection and inflammation.Conclusions: These findings indicate that serum markers of the humoral immune system and inflammation closely interact in response to infection or inflammation. Clustering analysis presented two main immune response components: an acute and an adaptive response, comprising markers of both biological pathways. Future studies should shift from single internal marker assessment to multiple humoral and inflammation serum markers combined, when assessing risk of clinical outcomes such as cancer.

scholarly journals Differences in DNA methylation of white blood cell types at birth and in adulthood reflect postnatal immune maturation and influence accuracy of cell type prediction

2018 ◽  
Author(s):  
Meaghan J Jones ◽  
Louie Dinh ◽  
Hamid Reza Razzaghian ◽  
Olivia de Goede ◽  
Julia L MacIsaac ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune System ◽  
Blood Cell ◽  
Cord Blood ◽  
White Blood Cell ◽  
Blood Cells ◽  
Cell Types ◽  
Cell Type ◽  
Cell Type Specific ◽  
The Impact

AbstractBackgroundDNA methylation profiling of peripheral blood leukocytes has many research applications, and characterizing the changes in DNA methylation of specific white blood cell types between newborn and adult could add insight into the maturation of the immune system. As a consequence of developmental changes, DNA methylation profiles derived from adult white blood cells are poor references for prediction of cord blood cell types from DNA methylation data. We thus examined cell-type specific differences in DNA methylation in leukocyte subsets between cord and adult blood, and assessed the impact of these differences on prediction of cell types in cord blood.ResultsThough all cell types showed differences between cord and adult blood, some specific patterns stood out that reflected how the immune system changes after birth. In cord blood, lymphoid cells showed less variability than in adult, potentially demonstrating their naïve status. In fact, cord CD4 and CD8 T cells were so similar that genetic effects on DNA methylation were greater than cell type effects in our analysis, and CD8 T cell frequencies remained difficult to predict, even after optimizing the library used for cord blood composition estimation. Myeloid cells showed fewer changes between cord and adult and also less variability, with monocytes showing the fewest sites of DNA methylation change between cord and adult. Finally, including nucleated red blood cells in the reference library was necessary for accurate cell type predictions in cord blood.ConclusionChanges in DNA methylation with age were highly cell type specific, and those differences paralleled what is known about the maturation of the postnatal immune system.

Reference Values for Selected Blood Parameters in Rabbits: Effects of Age and Physiological Status

2019 ◽  
Author(s):  
M. J. Argente ◽  
D. M. Abad-Salazar ◽  
E. M. Bermejo-González ◽  
M. L. Garcíaz ◽  
A. López-Palazón
Keyword(s):  
Animal Model ◽  
Immune System ◽  
Health Status ◽  
Blood Cells ◽  
White Blood Cells ◽  
Blood Parameters ◽  
Physiological Status ◽  
Immune Challenge ◽  
Leukocyte Counts ◽  
Over Time

Rabbit is widely used as an experimental animal model in infectious and non-infectious diseases. The haematologic data can be helpful in evaluating the health status of animals over time. The aim of this study was to determine the levels of red blood cells (RBC), white blood cells (WBC) and differential leukocyte counts in 5 nulliparous and 5 multiparous females, i.e. in young and older animals, at mating and at delivery. The values of RBC did not change with age, but WBC and lymphocytes decreased with age, a -33% and a -60% less in multiparous females than nulliparous ones. Monocytes count was double at delivery than at mating. In conclusion, aging on the immune system is manifested as reduction in production of mature lymphocytes and as a result, older females would not respond to immune challenge as robustly as the young ones. Physiological status is only related to production of monocytes.

scholarly journals Electrodeformation of White Blood Cells Enriched with Gold Nanoparticles

2021 ◽  
Author(s):  
Nicholas G. Hallfors ◽  
Jeremy M. Teo ◽  
Peter Bertone ◽  
Chakra Joshi ◽  
Ajymurat Orozaliev ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Immune System ◽  
Blood Cells ◽  
Microelectrode Array ◽  
White Blood Cells ◽  
Valuable Insight ◽  
System Activity ◽  
Combined Use ◽  
Insight Into

The elasticity of white blood cells (WBCs) provides valuable insight into the condition of the cells themselves, the presence of some diseases, as well as immune system activity. In this work, we describe a novel process of refined control of WBCs elasticity through a combined use of gold nanoparticles (AuNPs) and the microelectrode array device. The capture and controlled deformation of gold nanoparticles enriched white blood cells in vitro are demonstrated and quantified. Gold nanoparticles enhance the effect of electrically induced deformation and make the DEP related processes more controllable.

scholarly journals Gene expressions involved in immune system control and serum CA125 content in polycythemia vera. Tap

2020 ◽  
Vol 42 (1) ◽  
Author(s):  
Do Thi Trang ◽  
Nguyen Thi Xuan
Keyword(s):  
Immune System ◽  
Polycythemia Vera ◽  
Immune Tolerance ◽  
Blood Cells ◽  
Myeloproliferative Neoplasms ◽  
Tyrosine Phosphatase ◽  
White Blood Cells ◽  
System Control ◽  
Gene Expressions ◽  
Gene Group

Polycythemia Vera (PV) is a slowly progressing blood cancer associated with myeloproliferative neoplasms. The disease is characterized by an abnormal proliferation of three cell types including red blood cells, white blood cells and platelets and a symptom of pruritus caused by release of itching agents of activated mast cells. The enhanced expression of several genes involved in immune system control including CTLA-4, PD-1 and LAG3 are linked to activation immune tolerance. Klotho gene has anti-aging, anti-inflammation and anti-cancer functions. The SHP gene group belongs to the tyrosine phosphatase protein signaling family that regulates cancer cell proliferation through maturation, migration and apoptosis and includes two main genes, SHP-1 and SHP-2. The increased serum content of cancer antigen CA125 is considered as a cancer marker of several blood and hematopoietic disorders. In this study, we conducted experiments to determine mRNA expression of above genes in PV patients by realtime-PCR and CA125 concentration by ELISA. Results showed that expression of klotho, LAG3, CTLA-4 and PD-1 genes was decreased in PV patients, indicating that the immune tolerance was inactivated in PV patients. CA125 concentration was significantly increased in PV patients compared to healthy individuals and interestingly, there was a positive association among three patients, who having increased CA125 concentration and biochemical indicators including LDH, AST and ALT. The results in this study provide an important reference document for further studies that serve for the early detection of PV disease. 

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