Siglecs that Associate with DAP12

Angata, Takashi

doi:10.1007/978-981-15-1580-4_9

Cited by 24 publications

(15 citation statements)

References 67 publications

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“…Shown in Fig. 5e is an example of binding for Siglec-1 to Neu5Acα2-3Lac (2), where the complex is clearly resolved. Titrating the concentration of ligand enabled the K D values to be determined ( Fig.…”

Section: Siglec-fc Bindingmentioning

confidence: 99%

“…As a rapidly evolving family, there are 15 Siglecs in humans, while mice only have 9 Siglecs. The majority of Siglecs are inhibitory, dampening immune cell signaling through immunoreceptor tyrosine-based inhibitory motifs (ITIMs) within their cytoplasmic domain 2 . Importantly, the immunomodulatory properties of Siglecs are regulated by interactions with sialic acid-containing glycoconjugates, which can be either on the same (cis) cell or opposing (trans) cell or particle.…”

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confidence: 99%

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A versatile soluble siglec scaffold for sensitive and quantitative detection of glycan ligands

et al. 2020

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Sialic acid-binding immunoglobulin-type lectins (Siglecs) are immunomodulatory receptors that are regulated by their glycan ligands. The connections between Siglecs and human disease motivate improved methods to detect Siglec ligands. Here, we describe a new versatile set of Siglec-Fc proteins for glycan ligand detection. Enhanced sensitivity and selectivity are enabled through multimerization and avoiding Fc receptors, respectively. Using these Siglec-Fc proteins, Siglec ligands are systematically profiled on healthy and cancerous cells and tissues, revealing many unique patterns. Additional features enable the production of small, homogenous Siglec fragments and development of a quantitative ligand-binding mass spectrometry assay. Using this assay, the ligand specificities of several Siglecs are clarified. For CD33 (Siglec-3), we demonstrate that it recognizes both α2-3 and α2-6 sialosides in solution and on cells, which has implications for its link to Alzheimer’s disease susceptibility. These soluble Siglecs reveal the abundance of their glycan ligands on host cells as self-associated molecular patterns.

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Section: Siglec-fc Bindingmentioning

confidence: 99%

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confidence: 99%

A versatile soluble siglec scaffold for sensitive and quantitative detection of glycan ligands

et al. 2020

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“…Among the Siglec family members, the paired receptors, Siglec-5/14 and Siglec-11/16, display extremely similar extracellular ligand-binding regions and comparable cellular distribution resulting in the same ligand recognition ability whereas the diverse intracellular signalling pathways trigger the opposite effects. While the expression of inhibitory receptors was described in several human pathologies, the role of activatory counterparts is not fully understood [18]. However, recent advances in glycoimmunology suggest that targeting Siglec-sialoglycans checkpoint axis might be useful in the control of cancer immune evasion [19,20].…”

Section: Introductionmentioning

confidence: 99%

The Paired Siglecs in Brain Tumours Therapy: The Immunomodulatory Effect of Dexamethasone and Temozolomide in Human Glioma In Vitro Model

Wielgat

Wawrusiewicz‐Kurylonek

Czarnomysy

et al. 2021

IJMS

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The paired sialic acid-binding immunoglobulin like lectins (Siglecs) are characterized by similar cellular distribution and ligand recognition but opposing signalling functions attributed to different intracellular sequences. Since sialic acid—Siglec axis are known to control immune homeostasis, the imbalance between activatory and inhibitory mechanisms of glycan-dependent immune control is considered to promote pathology. The role of sialylation in cancer is described, however, its importance in immune regulation in gliomas is not fully understood. The experimental and clinical observation suggest that dexamethasone (Dex) and temozolomide (TMZ), used in the glioma management, alter the immunity within the tumour microenvironment. Using glioma-microglia/monocytes transwell co-cultures, we investigated modulatory action of Dex/TMZ on paired Siglecs. Based on real-time PCR and flow cytometry, we found changes in SIGLEC genes and their products. These effects were accompanied by altered cytokine profile and immune cells phenotype switching measured by arginases expression. Additionally, the exposure to Dex or TMZ increased the binding of inhibitory Siglec-5 and Siglec-11 fusion proteins to glioma cells. Our study suggests that the therapy-induced modulation of the interplay between sialoglycans and paired Siglecs, dependently on patient’s phenotype, is of particular signification in the immune surveillance in the glioma management and may be useful in glioma patient’s therapy plan verification.

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“…The DAP12 carries an intracellular ITAM and can trigger a signaling cascade via SYK, similar to the CLR Dectin-1 or Dectin-2. Siglec H is transducing its signal in rodents via DAP12 (58).…”

Section: Siglec -Glycoreceptors Binding To Sialylated Antigensmentioning

confidence: 99%

The Role of Lectin Receptors and Their Ligands in Controlling Allergic Inflammation

Peters

2021

Front. Immunol.

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More than fifty c-type lectin receptors (CLR) are known and have been identified so far. Moreover, we know the group of galectins and sialic acid-binding immunoglobulin-type lectins that also belong to the carbohydrate-binding receptors of the immune system. Thus, the lectin receptors form the largest receptor family among the pathogen recognition receptors. Similar to the toll-like receptors (TLRs), the CLR do not only recognize foreign but also endogenous molecules. In contrast to TLRs, which have a predominantly activating effect on the immune system, lectin receptors also mediate inhibitory signals. They play an important role in innate and adaptive immunity for the induction, regulation and shaping of the immune response. The hygiene hypothesis links enhanced infection to protection from allergic disease. Yet, the microbial substances that are responsible for mediating this allergy-protective activity still have to be identified. Microbes contain both ligands binding to TLRs and carbohydrates that are recognized by CLR and other lectin receptors. In the current literature, the CLR are often recognized as the ‘bad guys’ in allergic inflammation, because some glycoepitopes of allergens have been shown to bind to CLR, facilitating their uptake and presentation. On the other hand, there are many reports revealing that sugar moieties are involved in immune regulation. In this review, we will summarize what is known about the role of carbohydrate interaction with c-type lectins and other sugar-recognizing receptors in anti-inflammation, with a special focus on the regulation of the allergic immune response.

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Siglecs that Associate with DAP12

Cited by 24 publications

References 67 publications

A versatile soluble siglec scaffold for sensitive and quantitative detection of glycan ligands

A versatile soluble siglec scaffold for sensitive and quantitative detection of glycan ligands

The Paired Siglecs in Brain Tumours Therapy: The Immunomodulatory Effect of Dexamethasone and Temozolomide in Human Glioma In Vitro Model

The Role of Lectin Receptors and Their Ligands in Controlling Allergic Inflammation

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