Deacetylated sialic acids modulates immune mediated cytotoxicity via the sialic acid-Siglec pathway

Grabenstein, Susan; Barnard, Karen N.; Anim, Mathias Tawiah; Armoo, Albert; Weichert, Wendy S.; Bertozzi, Carolyn R.; Parrish, Colin R.; Willand‐Charnley, Rachel

doi:10.1093/glycob/cwab068

Cited by 17 publications

(15 citation statements)

References 56 publications

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“…In other words, high expression of SIAE promotes lung adenocarcinoma progression. Our study found that SIAE is a risk factor for SCLC ( 56 ). HIST1H2AL encodes a core histone protein, which was identified in this study with a better prognosis of SCLC ( 57 ).…”

Section: Discussionsupporting

confidence: 55%

Identifying diagnostic markers and constructing a prognostic model for small-cell lung cancer based on blood exosome-related genes and machine-learning methods

Zhang

Zhang²,

Wang³

et al. 2022

Front. Oncol.

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BackgroundSmall-cell lung cancer (SCLC) usually presents as an extensive disease with a poor prognosis at the time of diagnosis. Exosomes are rich in biological information and have a powerful impact on tumor progression and metastasis. Therefore, this study aimed to screen for diagnostic markers of blood exosomes in SCLC patients and to build a prognostic model.MethodsWe identified blood exosome differentially expressed (DE) RNAs in the exoRBase cohort and identified feature RNAs by the LASSO, Random Forest, and SVM-REF three algorithms. Then, we identified DE genes (DEGs) between SCLC tissues and normal lung tissues in the GEO cohort and obtained exosome-associated DEGs (EDEGs) by intersection with exosomal DEmRNAs. Finally, we performed univariate Cox, LASSO, and multivariate Cox regression analyses on EDEGs to construct the model. We then compared the patients’ overall survival (OS) between the two risk groups and assessed the independent prognostic value of the model using receiver operating characteristic (ROC) curve analysis.ResultsWe identified 952 DEmRNAs, 210 DElncRNAs, and 190 DEcircRNAs in exosomes and identified 13 feature RNAs with good diagnostic value. Then, we obtained 274 EDEGs and constructed a risk model containing 7 genes (TBX21, ZFHX2, HIST2H2BE, LTBP1, SIAE, HIST1H2AL, and TSPAN9). Low-risk patients had a longer OS time than high-risk patients. The risk model can independently predict the prognosis of SCLC patients with the areas under the ROC curve (AUCs) of 0.820 at 1 year, 0.952 at 3 years, and 0.989 at 5 years.ConclusionsWe identified 13 valuable diagnostic markers in the exosomes of SCLC patients and constructed a new promising prognostic model for SCLC.

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Section: Discussionsupporting

confidence: 55%

Identifying diagnostic markers and constructing a prognostic model for small-cell lung cancer based on blood exosome-related genes and machine-learning methods

Zhang

Zhang²,

Wang³

et al. 2022

Front. Oncol.

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“…Specific SA linkages, membrane distribution, and SA acetylation might be an important aspect of SA-dependent communication and signalling. In fact, studies using CRISPR Cas9 showed that SA acetylation affects Siglec-mediated functions (54). Besides, the predominant sialic acids on murine cells are N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), the latter not synthesised in humans because of the loss of the CMAH gene.…”

Section: Discussionmentioning

confidence: 99%

Synovial Fibroblast Sialylation Regulates Cell Migration and Activation of Inflammatory Pathways in Arthritogenesis

et al. 2022

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Synovial fibroblasts have emerged as critical underlying factors to perpetuate chronic joint inflammation in Rheumatoid Arthritis. Like any other cell, synovial fibroblasts are covered with a complex layer of glycans that can change in response to extracellular signals, such as inflammation. We have previously shown that inflammatory synovial fibroblasts show decreased levels of sialic acid, but our understanding of sialic acid-dependent pathophysiological pathways in these stromal cells is still very limited. In this report, we used in vivo and in vitro studies with exogenous sialidases and RNA sequencing to investigate the responses of murine synovial fibroblasts upon desialylation. Our results show that hyposialylated fibroblasts present a dysregulated migratory ability and an activated phenotype characterized by the expression of inflammatory mediators, such as cytokines and chemokines, and anti-viral related mechanisms. Removal of surface sialic acid also affected the expression of sialyltransferases, revealing the existence of a positive feedback to sustain reduced sialylation. Moreover, we demonstrate that synovial fibroblasts subsets have distinct sialyltransferase expression profiles, both in healthy and arthritic mice. These findings underline the ability of sialic acid to modulate homeostatic and inflammatory responses in non-immune synovial fibroblasts, suggesting that sialylation plays a key role in perpetuating local inflammation in the arthritic joint.

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“…In addition to being exploited by numerous microbes for attachment [2], sialic acids regulate host tolerance and immune activation by interactions with siglec-expressing immune cells [12][13][14]39]. These interactions can be modulated by sialic acid O-acetylation [40][41][42]. Sialic acid de-acetylation, which we have identified on erythrocyte and vascular surfaces in ISAV infected fish, typically enhances siglec interactions [40], and the biological end-result will depend on the specific siglec and cell type involved.…”

Section: First Does the Rde-induced Cell Surface-modulation Influence...mentioning

confidence: 91%

The infectious salmon anaemia virus esterase prunes erythrocyte surfaces in infected Atlantic salmon and exposes terminal sialic acids to lectin recognition

Hol

Andresen

Ploss

et al. 2023

Preprint

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Many sialic acid-binding viruses express a receptor-destroying enzyme (RDE) that removes the virus-targeted receptor and limits viral interactions with the host cell surface. Despite a growing appreciation of how the viral RDE promotes viral fitness, little is known about its direct effects on the host. Infectious salmon anaemia virus (ISAV) attaches to 4-O-acetylated sialic acids on the surface of Atlantic salmon epithelial, endothelial, and red blood cells. ISAV receptor binding and destruction are effectuated by the same surface molecule, the haemagglutinin esterase (HE). We recently discovered a global loss of vascular 4-O-acetylated sialic acids in ISAV-infected fish. The loss correlated with the expression of viral proteins, giving rise to the hypothesis that it was mediated by the HE. Here, we report that the capacity to bind new ISAV particles is also progressively lost from circulating erythrocytes in infected fish. Furthermore, salmon erythrocytes exposed to ISAV ex vivo lost their capacity to bind new ISAV particles. The loss of ISAV binding was not associated with receptor saturation. Moreover, upon loss of the ISAV receptor, erythrocyte surfaces became more available to the lectin wheat germ agglutinin, suggesting a potential to alter interactions with endogenous lectins of similar specificity. The pruning of erythrocyte surfaces was inhibited by an antibody that prevented ISAV attachment. Furthermore, recombinant HE, but not an esterase-silenced mutant, was sufficient to induce the observed surface modulation. Our results directly link the ISAV-induced erythrocyte modulation to the hydrolytic activity of the HE and show that the observed effects are not mediated by endogenous esterases. Our findings are the first to directly link a viral esterase to extensive host cell surface modulation in infected individuals. This raises the question of how common the phenomenon is among sialic acid-binding viruses. It is also relevant to ask if the altered sialic acid landscape of the affected cells influences host biological functions with relevance to viral disease.

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Deacetylated sialic acids modulates immune mediated cytotoxicity via the sialic acid-Siglec pathway

Cited by 17 publications

References 56 publications

Identifying diagnostic markers and constructing a prognostic model for small-cell lung cancer based on blood exosome-related genes and machine-learning methods

Identifying diagnostic markers and constructing a prognostic model for small-cell lung cancer based on blood exosome-related genes and machine-learning methods

Synovial Fibroblast Sialylation Regulates Cell Migration and Activation of Inflammatory Pathways in Arthritogenesis

The infectious salmon anaemia virus esterase prunes erythrocyte surfaces in infected Atlantic salmon and exposes terminal sialic acids to lectin recognition

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