Sialic Acid-Binding Immunoglobulin-like Lectin G Promotes Atherosclerosis and Liver Inflammation by Suppressing the Protective Functions of B-1 Cells
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-...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716301309 |
| _version_ | 1818381986957361152 |
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| author | Sabrina Gruber Tim Hendrikx Dimitrios Tsiantoulas Maria Ozsvar-Kozma Laura Göderle Ziad Mallat Joseph L. Witztum Ronit Shiri-Sverdlov Lars Nitschke Christoph J. Binder |
| author_facet | Sabrina Gruber Tim Hendrikx Dimitrios Tsiantoulas Maria Ozsvar-Kozma Laura Göderle Ziad Mallat Joseph L. Witztum Ronit Shiri-Sverdlov Lars Nitschke Christoph J. Binder |
| author_sort | Sabrina Gruber |
| collection | DOAJ |
| description | 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. We further demonstrate that selective deficiency of Siglec-G in B cells alone is sufficient to mediate these effects. Levels of B-1 cell-derived natural IgM with specificity for OxLDL were significantly increased in the plasma and peritoneal cavity of Siglec-G-deficient mice. Consistent with the neutralizing functions of OxLDL-specific IgM, Siglec-G-deficient mice were protected from OxLDL-induced sterile inflammation. Thus, Siglec-G promotes atherosclerosis and hepatic inflammation by suppressing protective anti-inflammatory effector functions of B cells. |
| first_indexed | 2024-12-14T02:43:18Z |
| format | Article |
| id | doaj.art-2a2ee23df4b14c93b9003136830ada8a |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-14T02:43:18Z |
| publishDate | 2016-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-2a2ee23df4b14c93b9003136830ada8a2022-12-21T23:19:57ZengElsevierCell Reports2211-12472016-03-0114102348236110.1016/j.celrep.2016.02.027Sialic Acid-Binding Immunoglobulin-like Lectin G Promotes Atherosclerosis and Liver Inflammation by Suppressing the Protective Functions of B-1 CellsSabrina Gruber0Tim Hendrikx1Dimitrios Tsiantoulas2Maria Ozsvar-Kozma3Laura Göderle4Ziad Mallat5Joseph L. Witztum6Ronit Shiri-Sverdlov7Lars Nitschke8Christoph J. Binder9CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, AustriaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, AustriaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, AustriaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, AustriaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, AustriaDivision of Cardiovascular Medicine, Department of Medicine, University of Cambridge, CB2 0SZ Cambridge, UKDivision of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, CA 92110, USADepartment of Molecular Genetics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6229 ER Maastricht, the NetherlandsDivision of Genetics, Department of Biology, University of Erlangen-Nuremberg, 91058 Erlangen, GermanyCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, AustriaAtherosclerosis 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. We further demonstrate that selective deficiency of Siglec-G in B cells alone is sufficient to mediate these effects. Levels of B-1 cell-derived natural IgM with specificity for OxLDL were significantly increased in the plasma and peritoneal cavity of Siglec-G-deficient mice. Consistent with the neutralizing functions of OxLDL-specific IgM, Siglec-G-deficient mice were protected from OxLDL-induced sterile inflammation. Thus, Siglec-G promotes atherosclerosis and hepatic inflammation by suppressing protective anti-inflammatory effector functions of B cells.http://www.sciencedirect.com/science/article/pii/S2211124716301309 |
| spellingShingle | Sabrina Gruber Tim Hendrikx Dimitrios Tsiantoulas Maria Ozsvar-Kozma Laura Göderle Ziad Mallat Joseph L. Witztum Ronit Shiri-Sverdlov Lars Nitschke Christoph J. Binder Sialic Acid-Binding Immunoglobulin-like Lectin G Promotes Atherosclerosis and Liver Inflammation by Suppressing the Protective Functions of B-1 Cells Cell Reports |
| title | Sialic Acid-Binding Immunoglobulin-like Lectin G Promotes Atherosclerosis and Liver Inflammation by Suppressing the Protective Functions of B-1 Cells |
| title_full | Sialic Acid-Binding Immunoglobulin-like Lectin G Promotes Atherosclerosis and Liver Inflammation by Suppressing the Protective Functions of B-1 Cells |
| title_fullStr | Sialic Acid-Binding Immunoglobulin-like Lectin G Promotes Atherosclerosis and Liver Inflammation by Suppressing the Protective Functions of B-1 Cells |
| title_full_unstemmed | Sialic Acid-Binding Immunoglobulin-like Lectin G Promotes Atherosclerosis and Liver Inflammation by Suppressing the Protective Functions of B-1 Cells |
| title_short | Sialic Acid-Binding Immunoglobulin-like Lectin G Promotes Atherosclerosis and Liver Inflammation by Suppressing the Protective Functions of B-1 Cells |
| title_sort | sialic acid binding immunoglobulin like lectin g promotes atherosclerosis and liver inflammation by suppressing the protective functions of b 1 cells |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716301309 |
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