Sialic acid–binding Ig‐like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus

Biesen, Robert; Demir, Cemal; Barkhudarova, Fidan; Grün, Joachim R.; Steinbrich-Zöllner, Marta; Backhaus, Marina; Häupl, Thomas; Rudwaleit, Martín; Riemekasten, Gabriela; Radbruch, Andreas; Hiepe, Falk; Burmester, Gerd‐Rüdiger; Grützkau, Andreas

doi:10.1002/art.23404

Cited by 175 publications

(168 citation statements)

References 45 publications

(60 reference statements)

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“…However, none of these genes were significantly downregulated in vivo in whole blood from RSV‐infected infants (data not shown). Upregulation of Siglec‐1 on monocytes has been observed in patients with atherosclerosis, systemic sclerosis, rheumatoid arthritis, systemic lupus erythematous and human immunodeficiency virus infections 19, 20, 21, 22, 23. The common denominator in these studies appears to be type I interferons (IFNs).…”

Section: Discussionmentioning

confidence: 99%

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

et al. 2018

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Interferon gamma (IFN‐γ) plays an important role in the antiviral immune response during respiratory syncytial virus (RSV) infections. Monocytes and T cells are recruited to the site of RSV infection, but it is unclear whether cell‐cell interactions between monocytes and T cells regulate IFN‐γ production. In this study, micro‐array data identified the upregulation of sialic acid‐binding immunoglobulin‐type lectin 1 (Siglec‐1) in human RSV‐infected infants. In vitro, RSV increased expression of Siglec‐1 on healthy newborn and adult monocytes. RSV‐induced Siglec‐1 on monocytes inhibited IFN‐γ production by adult CD4+ T cells. In contrast, IFN‐γ production by RSV in newborns was not affected by Siglec‐1. The ligand for Siglec‐1, CD43, is highly expressed on adult CD4+ T cells compared to newborns. Our data show that Siglec‐1 reduces IFN‐γ release by adult T cells possibly by binding to the highly expressed CD43. The Siglec‐1‐dependent inhibition of IFN‐γ in adults and the low expression of CD43 on newborn T cells provides a better understanding of the immune response against RSV in early life and adulthood.

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Section: Discussionmentioning

confidence: 99%

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

et al. 2018

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“…They have also been found in transplant tissues (35). One potential explanation for the presence of SnL + Tregs in fresh splenocytes is that this subset could + -resident and inflammatory monocytes were found in PBMCs of patients with SLE and correlated to disease severity and other established biomarkers of the disease (11). Despite such a close association between Sn and disease activity, it remains unclear whether Sn might actively be involved in the pathogenesis of SLE.…”

Section: Discussionmentioning

confidence: 99%

“…Under inflammatory conditions, Sn can be strongly upregulated on macrophages, as observed in autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) (9) and human rheumatoid arthritis (6). Sn is normally undetectable *Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom; on circulating monocytes, but is induced on these cells in patients with HIV infection (10), systemic lupus erythematosus (SLE) (11), and systemic sclerosis (12) in a type I IFN-dependent manner.…”

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confidence: 99%

Sialoadhesin Ligand Expression Identifies a Subset of CD4+Foxp3− T Cells with a Distinct Activation and Glycosylation Profile

Kidder

Richards

Ziltener³

et al. 2013

The Journal of Immunology

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Sialoadhesin (Sn) is a sialic acid–binding Ig-like lectin expressed selectively on macrophage subsets. In a model of experimental autoimmune encephalomyelitis, Sn interacted with sialylated ligands expressed selectively on CD4+Foxp3+ regulatory T cells (Tregs) and inhibited their proliferation. In this study, we examined the induction of Sn ligands (SnL) on all splenic CD4+ T cells following in vitro activation. Most CD4+ Tregs strongly upregulated SnL, whereas only a small subset of ∼20% CD4+Foxp3− T cells (effector T cells [Teffs]) upregulated SnL. SnL+ Teffs displayed higher levels of activation markers CD25 and CD69, exhibited increased proliferation, and produced higher amounts of IL-2 and IFN-γ than corresponding SnL− Teffs. Coculture of activated Teffs with Sn+ macrophages or Sn+ Chinese hamster ovary cells resulted in increased cell death, suggesting a regulatory role for Sn–SnL interactions. The key importance of α2,3-sialylation in SnL expression was demonstrated by increased binding of α2,3-linkage–specific Maackia amurensis lectin, increased expression of α2,3-sialyltransferase ST3GalVI, and loss of SnL following treatment with an α2,3-linkage–specific sialidase. The induction of SnL on activated CD4+ T cells was dependent on N-glycan rather than O-glycan biosynthesis and independent of the mucin-like molecules CD43 and P-selectin glycoprotein ligand-1, previously implicated in Sn interactions. Induction of ligands on CD4+Foxp3− Teffs was also observed in vivo using the New Zealand Black × New Zealand White F1 murine model of spontaneous lupus and SnL levels on Teffs correlated strongly with the degree of proteinuria. Collectively, these data indicate that SnL is a novel marker of activated CD4+ Teffs that are implicated in the pathogenesis of autoimmune diseases.

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“…Generation of complementary RNA, sample hybridization (using Affymetrix HG U133 plus 2.0 arrays), and scanning with a GeneChip Scanner 3000 (Affymetrix) were performed as described previously. 31 Data from 3 pairs of conditions were analyzed using the BioRetis database (supplemental Experimental Procedures). The chip data discussed in this publication have been deposited in the National Center for Biotechnology Information Gene Expression Omnibus database and are accessible through accession number GSE62693.…”

Section: Microarray Hybridization and Data Analysismentioning

confidence: 99%

miR-125b controls monocyte adaptation to inflammation through mitochondrial metabolism and dynamics

Duroux-Richard

Roubert

Ammari

et al. 2016

Blood

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Key Points• miR-125b reduces mitochondrial respiration and promotes elongation of mitochondrial network through BIK and MTP18 silencing, respectively. • The miR-125b/BIK/MTP18 axis promotes adaptation of monocytes to inflammation.Metabolic changes drive monocyte differentiation and fate. Although abnormal mitochondria metabolism and innate immune responses participate in the pathogenesis of many inflammatory disorders, molecular events regulating mitochondrial activity to control life and death in monocytes remain poorly understood. We show here that, in human monocytes, microRNA-125b (miR-125b) attenuates the mitochondrial respiration through the silencing of the BH3-only proapoptotic protein BIK and promotes the elongation of the mitochondrial network through the targeting of the mitochondrial fission process 1 protein MTP18, leading to apoptosis. Proinflammatory activation of monocyte-derived macrophages is associated with a concomitant increase in miR-125b expression and decrease in BIK and MTP18 expression, which lead to reduced oxidative phosphorylation and enhanced mitochondrial fusion. In a chronic inflammatory systemic disorder, CD14 1 blood monocytes display reduced miR-125b expression as compared with healthy controls, inversely correlated with BIK and MTP18 messenger RNA expression. Our findings not only identify BIK and MTP18 as novel targets for miR-125b that control mitochondrial metabolism and dynamics, respectively, but also reveal a novel function for miR-125b in regulating metabolic adaptation of monocytes to inflammation. Together, these data unravel new molecular mechanisms for a proapoptotic role of miR-125b in monocytes and identify potential targets for interfering with excessive inflammatory activation of monocytes in inflammatory disorders. (Blood. 2016;128(26): 3125-3136)

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Sialic acid–binding Ig‐like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus

Cited by 175 publications

References 45 publications

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

Sialoadhesin Ligand Expression Identifies a Subset of CD4+Foxp3− T Cells with a Distinct Activation and Glycosylation Profile

miR-125b controls monocyte adaptation to inflammation through mitochondrial metabolism and dynamics

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