Sialic Acid-Binding Immunoglobulin-like Lectin G Promotes Atherosclerosis and Liver Inflammation by Suppressing the Protective Functions of B-1 Cells

Publication date: Available online 3 March 2016
Source:Cell Reports
Author(s): 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. 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.

Graphical abstract

Teaser

Gruber et al. demonstrate that Siglec-G deficiency protects from oxidized LDL-induced inflammation through the expansion of B-1 cells secreting natural IgM antibodies, leading to reduced atherosclerosis and hepatic inflammation. CXCL1 represents a common pro-inflammatory factor that is reduced as a result of Siglec-G deficiency.


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