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Siglec-G

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https://www.readbyqxmd.com/read/29288201/murine-red-blood-cells-lack-ligands-for-b-cell-siglecs-allowing-strong-activation-by-erythrocyte-surface-antigens
#1
Fernando Spiller, Corwin M Nycholat, Chika Kikuchi, James C Paulson, Matthew S Macauley
CD22 and sialic acid-binding Ig-like lectin (Siglec)-G are members of the Siglec family of inhibitory coreceptors expressed on B cells that participate in enforcement of peripheral B cell tolerance. We have shown previously that when a BCR engages its cognate Ag on a cell surface that also expresses Siglec ligands, B cell Siglecs are recruited to the immunological synapse, resulting in suppression of BCR signaling and B cell apoptosis. Because all cells display sialic acids, and CD22 and Siglec-G have distinct, yet overlapping, specificities for sialic acid-containing glycan ligands, any cell could, in principle, invoke this tolerogenic mechanism for cell surface Ags...
February 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28819186/cd24-induces-changes-to-the-surface-receptors-of-b-cell-microvesicles-with-variable-effects-on-their-rna-and-protein-cargo
#2
D Craig Ayre, Ian C Chute, Andrew P Joy, David A Barnett, Andrew M Hogan, Marc P Grüll, Lourdes Peña-Castillo, Andrew S Lang, Stephen M Lewis, Sherri L Christian
The CD24 cell surface receptor promotes apoptosis in developing B cells, and we recently found that it induces B cells to release plasma membrane-derived, CD24-bearing microvesicles (MVs). Here we have performed a systematic characterization of B cell MVs released from WEHI-231 B lymphoma cells in response to CD24 stimulation. We found that B cells constitutively release MVs of approximately 120 nm, and that CD24 induces an increase in phosphatidylserine-positive MV release. RNA cargo is predominantly comprised of 5S rRNA, regardless of stimulation; however, CD24 causes a decrease in the incorporation of protein coding transcripts...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28757612/the-cd24-siglec-g-axis-protects-mice-against-cuprizone-induced-oligodendrocyte-loss-targeting-danger-signal-for-neuroprotection
#3
Ning Li, Pan Zheng, Yang Liu
No abstract text is available yet for this article.
January 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28724800/siglec-g-represses-damp-mediated-effects-on-t-cells
#4
Tomomi Toubai, Corinne Rossi, Katherine Oravecz-Wilson, Cynthia Zajac, Chen Liu, Thomas Braun, Hideaki Fujiwara, Julia Wu, Yaping Sun, Stuart Brabbs, Hiroya Tamaki, John Magenau, Pang Zheng, Yang Liu, Pavan Reddy
The role of negative regulators or suppressors of the damage-associated molecular pattern-mediated (DAMP-mediated) stimulation of innate immune responses is being increasingly appreciated. However, the presence and function of suppressors of DAMP-mediated effects on T cells, and whether they can be targeted to mitigate T cell-dependent immunopathology remain unknown. Sialic acid-binding immunoglobulin-like lectin G (Siglec-G) is a negative regulator of DAMP-mediated responses in innate immune cells, but its T cell-autonomous role is unknown...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/27624073/reduced-immune-response-to-polymeric-micelles-coating-sialic-acids
#5
Masashi Ohmae, Mei Kojima, Kenta Mihara, Yuji Yamazaki, Isao Hara, Eri Hara, Shunsaku Kimura
Effects of sialic acid coatings on polymeric micelle consisting of poly(sarcosine)-block-poly(l-lactic acid) (Lactosome) in the aim of prevention of the accelerated blood clearance (ABC) phenomenon are studied. Two kinds of the sialic acid-presenting Lactosomes targeting the immunosuppressive receptors of Siglec-G and CD22 have been successfully prepared. Lactosome presenting 5-N-acetylneuraminic acid or 5-N-acetylneuraminyl-α(2→6)-galactosyl-β(1→4)-N-acetylglucosamine at the nanocarrier surface diminished the ABC phenomenon due to the reduction of the anti-poly(sarcosine) IgM production...
October 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27548433/the-lectin-siglec-g-inhibits-dendritic-cell-cross-presentation-by-impairing-mhc-class-i-peptide-complex-formation
#6
Yuanyuan Ding, Zhenhong Guo, Yiqi Liu, Xia Li, Qian Zhang, Xiongfei Xu, Yan Gu, Yi Zhang, Dezhi Zhao, Xuetao Cao
CD8α(+) dendritic cells (DCs) are specialized at cross-presenting extracellular antigens on major histocompatibility complex (MHC) class I molecules to initiate cytotoxic T lymphocyte (CTL) responses; however, details of the mechanisms that regulate cross-presentation remain unknown. We found lower expression of the lectin family member Siglec-G in CD8α(+) DCs, and Siglec-G deficient (Siglecg(-/-)) mice generated more antigen-specific CTLs to inhibit intracellular bacterial infection and tumor growth. MHC class I-peptide complexes were more abundant on Siglecg(-/-) CD8α(+) DCs than on Siglecg(+/+) CD8α(+) DCs...
October 2016: Nature Immunology
https://www.readbyqxmd.com/read/27498179/pathogen-associated-porin-turns-il-10-competent-b-1a-cells-toward-proinflammatory-cytokine-response
#7
Amlan Kanti Ghosh, Debolina Sinha, Ratna Biswas, Tapas Biswas
Shigellosis is a major problem in the developing countries causing mortality and morbidity particularly among the children. Shigella spp. harbours the epithelial cells of the human colon to infect the host and spread the disease. We analyzed the response of B-1a cells, the major component of the mucosal immune system to porin of Shigella dysenteriae type 1. We show that porin while proliferating B-1a cells, deplete Siglec-G, the inhibitory molecule present on B-1a cells. Adjuvanticity of porin has been shown to govern innate signaling for promoting host adaptive immune response...
December 2016: Immunobiology
https://www.readbyqxmd.com/read/26947073/sialic-acid-binding-immunoglobulin-like-lectin-g-promotes-atherosclerosis-and-liver-inflammation-by-suppressing-the-protective-functions-of-b-1-cells
#8
Sabrina Gruber, Tim Hendrikx, Dimitrios Tsiantoulas, Maria Ozsvar-Kozma, Laura Göderle, Ziad Mallat, Joseph L Witztum, Ronit Shiri-Sverdlov, Lars Nitschke, Christoph J Binder
Atherosclerosis is initiated and sustained by hypercholesterolemia, which results in the generation of oxidized LDL (OxLDL) and other metabolic byproducts that trigger inflammation. Specific immune responses have been shown to modulate the inflammatory response during atherogenesis. The sialic acid-binding immunoglobulin-like lectin G (Siglec-G) is a negative regulator of the functions of several immune cells, including myeloid cells and B-1 cells. Here, we show that deficiency of Siglec-G in atherosclerosis-prone mice inhibits plaque formation and diet-induced hepatic inflammation...
March 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/26683151/sialic-acids-and-autoimmune-disease
#9
REVIEW
Vinay S Mahajan, Shiv Pillai
An important underlying mechanism that contributes to autoimmunity is the loss of inhibitory signaling in the immune system. Sialic acid-recognizing Ig superfamily lectins or Siglecs are a family of cell surface proteins largely expressed in hematopoietic cells. The majority of Siglecs are inhibitory receptors expressed in immune cells that bind to sialic acid-containing ligands and recruit SH2-domain-containing tyrosine phosphatases to their cytoplasmic tails. They deliver inhibitory signals that can contribute to the constraining of immune cells, and thus protect the host from autoimmunity...
January 2016: Immunological Reviews
https://www.readbyqxmd.com/read/26621719/amyloid-fibrils-activate-b-1a-lymphocytes-to-ameliorate-inflammatory-brain-disease
#10
Michael Phillip Kurnellas, Eliver Eid Bou Ghosn, Jill M Schartner, Jeanette Baker, Jesse J Rothbard, Robert S Negrin, Leonore A Herzenberg, C Garrison Fathman, Lawrence Steinman, Jonathan B Rothbard
Amyloid fibrils composed of peptides as short as six amino acids are therapeutic in experimental autoimmune encephalomyelitis (EAE), reducing paralysis and inflammation, while inducing several pathways of immune suppression. Intraperitoneal injection of fibrils selectively activates B-1a lymphocytes and two populations of resident macrophages (MΦs), increasing IL-10 production, and triggering their exodus from the peritoneum. The importance of IL-10-producing B-1a cells in this effective therapy was established in loss-of-function experiments where neither B-cell-deficient (μMT) nor IL10(-/-) mice with EAE responded to the fibrils...
December 8, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26194636/siglec-g-is-a-b-1-cell-inhibitory-receptor-and-also-controls-b-cell-tolerance
#11
REVIEW
Lars Nitschke
B cell antigen receptor signaling on B-1 cells is controlled by several inhibitory receptors, including Siglec-G, which is a member of the Siglec (sialic acid-binding immunoglobulin-like lectin) family and inhibits B cell signaling. The inhibitory function of Siglec-G is largely restricted to B-1 cells, as demonstrated by studies of Siglec-G-deficient mice showing a phenotype affecting mostly B-1 cells. Siglec-G-deficient mice show a markedly increased B-1a cell population, enhanced B-1 cell signaling, and a shift in the immunoglobulin repertoire secreted by their B-1 cells...
December 2015: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/25987743/siglec-g-deficiency-leads-to-autoimmunity-in-aging-c57bl-6-mice
#12
Jennifer Müller, Benjamin Lunz, Inessa Schwab, Andreas Acs, Falk Nimmerjahn, Christoph Daniel, Lars Nitschke
Siglec-G, a member of the sialic acid-binding Ig-like lectin (Siglec) family, is expressed on B cell and dendritic cell surfaces. It acts as an inhibitory coreceptor and modulates B cell activation, especially on B1 cells, as Siglec-G-deficient mice show mainly a B1 cell-restricted phenotype resulting in increased B1 cell numbers. Although higher B1 cell numbers are discussed to be associated with autoimmunity, loss of Siglec-G does not result in autoimmune disease in BALB/c mice. However, there is evidence from Siglec-G × CD22 double-deficient mice and Siglec-G(-/-) mice on an autoimmune-prone MRL/lpr background that Siglec-G is important to maintain tolerance in B cells...
July 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/25748019/il-15-temporally-reorients-il-10-biased-b-1a-cells-toward-il-12-expression
#13
Amlan Kanti Ghosh, Debolina Sinha, Subhadeep Mukherjee, Ratna Biswas, Tapas Biswas
Interleukin (IL)-15 is known to strongly modulate T-cell function; however, its role in controlling mucosal immunity, including its ability to modulate B-1a cell activity, remains to be elucidated. Here, we show that IL-15 upregulates activation molecules and the costimulatory molecule CD80 on viable B-1a cells. Cell activation was accompanied by the depletion of sialic acid-binding immunoglobulin-like lectin (Siglec)-G, an inhibitor of cell activation that is present on B-1a cells. The IL-15 receptor CD122 was stimulated on B-1a cells by the cytokine showing its direct involvement in IL-15-mediated responses...
March 2016: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/25252961/siglecs-induce-tolerance-to-cell-surface-antigens-by-bim-dependent-deletion-of-the-antigen-reactive-b-cells
#14
Matthew S Macauley, James C Paulson
Infusion of blood cells from a donor can induce humoral tolerance in a recipient and increase the probability of successful organ transplant, a clinical method defined as donor-specific transfusion (DST). Despite the clinical success of DST, the immunological mechanisms by which blood cells displaying a foreign Ag induce tolerance remain poorly understood. Based on recent findings showing that the B cell siglecs, CD22 and Siglec-G, can promote tolerance to Ags presented on the same surface as their ligands, we speculated that the B cell siglecs are key players in tolerance induced by DST...
November 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/25187624/broad-and-direct-interaction-between-tlr-and-siglec-families-of-pattern-recognition-receptors-and-its-regulation-by-neu1
#15
Guo-Yun Chen, Nicholas K Brown, Wei Wu, Zahra Khedri, Hai Yu, Xi Chen, Diantha van de Vlekkert, Alessandra D'Azzo, Pan Zheng, Yang Liu
Both pathogen- and tissue damage-associated molecular patterns induce inflammation through toll-like receptors (TLRs), while sialic acid-binding immunoglobulin superfamily lectin receptors (Siglecs) provide negative regulation. Here we report extensive and direct interactions between these pattern recognition receptors. The promiscuous TLR binders were human SIGLEC-5/9 and mouse Siglec-3/E/F. Mouse Siglec-G did not show appreciable binding to any TLRs tested. Correspondingly, Siglece deletion enhanced dendritic cell responses to all microbial TLR ligands tested, while Siglecg deletion did not affect the responses to these ligands...
September 3, 2014: ELife
https://www.readbyqxmd.com/read/25002414/cd22-and-siglec-g-regulate-inhibition-of-b-cell-signaling-by-sialic-acid-ligand-binding-and-control-b-cell-tolerance
#16
REVIEW
Lars Nitschke
CD22 and Siglec-G are two B-cell expressed members of the Siglec (sialic acid-binding immunoglobulin (Ig)-like lectin) family and are potent inhibitors of B-cell signaling. Genetic approaches have provided evidence that this inhibition of B-cell antigen receptor (BCR) signaling by Siglecs is dependent on ligand binding to sialic acids in specific linkages. The cis-ligand-binding activity of CD22 leads to homo-oligomer formation, which are to a large extent found in membrane domains that are distinct from those containing the BCR...
September 2014: Glycobiology
https://www.readbyqxmd.com/read/24996822/siglec-g-10-in-self-nonself-discrimination-of-innate-and-adaptive-immunity
#17
REVIEW
Guo-Yun Chen, Nicholas K Brown, Pan Zheng, Yang Liu
Siglec-G/10 is broadly expressed on B cells, dendritic cells and macrophage subsets. It binds strongly to CD24, a small glycosyl-phosphatidylinositol-anchored sialoprotein, in a sialylation-dependent manner. Targeted mutation of Siglecg dramatically elevates the level of natural IgM antibodies and its producer, B1 B cells. Incorporation of Siglec-G ligands to both T-dependent and T-independent immunogens reduces antibody production and induces B-cell tolerance to subsequent antigen challenges. By interacting with CD24, Siglec-G suppresses inflammatory responses to danger (damage)-associated molecular patterns, such as heat-shock proteins and high mobility group protein 1, but not to Toll-like receptor ligands...
September 2014: Glycobiology
https://www.readbyqxmd.com/read/24929000/a-balance-between-b-cell-receptor-and-inhibitory-receptor-signaling-controls-plasma-cell-differentiation-by-maintaining-optimal-ets1-levels
#18
Wei Luo, Jessica Mayeux, Toni Gutierrez, Lisa Russell, Andrew Getahun, Jennifer Müller, Thomas Tedder, Jane Parnes, Robert Rickert, Lars Nitschke, John Cambier, Anne B Satterthwaite, Lee Ann Garrett-Sinha
Signaling through the BCR can drive B cell activation and contribute to B cell differentiation into Ab-secreting plasma cells. The positive BCR signal is counterbalanced by a number of membrane-localized inhibitory receptors that limit B cell activation and plasma cell differentiation. Deficiencies in these negative signaling pathways may cause autoantibody generation and autoimmune disease in both animal models and human patients. We have previously shown that the transcription factor Ets1 can restrain B cell differentiation into plasma cells...
July 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/24876528/siglec-g-signaling-dampens-gvhd
#19
COMMENT
Robert Zeiser
No abstract text is available yet for this article.
May 29, 2014: Blood
https://www.readbyqxmd.com/read/24859880/siglec-g-deficiency-increases-susceptibility-to-develop-b-cell-lymphoproliferative-disorders
#20
Giorgia Simonetti, Maria Teresa Sabrina Bertilaccio, Tania Veliz Rodriguez, Benedetta Apollonio, Antonis Dagklis, Martina Rocchi, Anna Innocenzi, Stefano Casola, Thomas H Winkler, Lars Nitschke, Maurilio Ponzoni, Federico Caligaris-Cappio, Paolo Ghia
The sialic-acid-binding immunoglobulin-like lectin SIGLEC-G is a negative regulator of B-cell receptor-mediated calcium signaling. Its deficiency leads to reduced turnover and increased proliferation and survival of murine B-1a cells. Siglecg(-/-) mice show a premature expansion of polyclonal CD5(+) B cells in the spleen and the peritoneal cavity. Here we studied the fate of B lymphocytes in Siglecg(-/-) mice over time. We demonstrate that in aging animals SIGLEC-G deficiency promotes progressive accumulation of monoclonal B lymphocytes and increases the susceptibility to develop B-cell lymphoproliferative disorders...
August 2014: Haematologica
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