title: Sialic Acid-Binding Immunoglobulin-like Lectin G Promotes Atherosclerosis and Liver Inflammation by Suppressing the Protective Functions of B-1 Cells.
abstract: 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.
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Gruber
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria; Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6229 ER Maastricht, the Netherlands.
authors.forename: Tim
authors.initials: T
authors.lastname: Hendrikx
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsiantoulas
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Ozsvar-Kozma
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Laura
authors.initials: L
authors.lastname: Göderle
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, CB2 0SZ Cambridge, UK.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Mallat
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, CA 92110, USA.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.affiliation: Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6229 ER Maastricht, the Netherlands.
authors.forename: Ronit
authors.initials: R
authors.lastname: Shiri-Sverdlov
authors.affiliation: Division of Genetics, Department of Biology, University of Erlangen-Nuremberg, 91058 Erlangen, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria. Electronic address: christoph.binder@meduniwien.ac.at.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Binder
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000032:analysis / Q000097:blood; D016207:Cytokines / Q000032:analysis / Q000097:blood; D059305:Diet, High-Fat; D007118:Immunoassay; D007075:Immunoglobulin M / Q000097:blood; D007249:Inflammation / Q000473:pathology; D037102:Lectins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010538:Peritonitis / Q000517:prevention & control / Q000662:veterinary; D012333:RNA, Messenger / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D000685:Serum Amyloid A Protein / Q000032:analysis; D063265:Sialic Acid Binding Immunoglobulin-like Lectins
chemical_list: D018925:Chemokines; D016207:Cytokines; D007075:Immunoglobulin M; D037102:Lectins; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D011973:Receptors, LDL; D000685:Serum Amyloid A Protein; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C522403:Siglecg protein, mouse; C099252:oxidized low density lipoprotein; D017493:Leukocyte Common Antigens