Galectin-9: A novel promoter of atherosclerosis progression.

BACKGROUND AND AIMS: Atherosclerosis is widely accepted to be an inflammatory disease driven by lipid accumulation and leukocyte recruitment. More recently, galectins, a family of ß-galactoside binding proteins, have been shown to play a role in leukocyte recruitment among other immunomodulatory functions. Galectin (Gal) -9, a tandem repeat type galectin expressed by the endothelium in inflammatory environments, has been proposed to promote leukocyte recruitment. However, the role of Gal-9 in the context of monocyte recruitment remains elusive. METHODS AND RESULTS: Here, we characterise the immunomodulatory role of Gal-9 in context of atherosclerosis. We show that ApoE-/-Gal-9-/- mice have a significantly reduced aortic plaque burden compared to their ApoE-/- littermate controls after 12 weeks of high fat diet. RNA sequencing data from two independent studies reveal Lgals9 expression in leukocyte clusters isolated from murine atherosclerotic plaques. Additionally, soluble Gal-9 protein induces monocyte activation and a pro-inflammatory phenotype in macrophages. Furthermore, we show that immobilised recombinant Gal-9 acts as capture and adhesion molecule for CD14+ monocytes in a ß2-integrin and glycan dependent manner, while adhesion of monocytes to stimulated endothelium is reduced when Gal-9 is knocked down. Gal-9 also facilitates enhanced recruitment of leukocytes from peripheral arterial disease (PAD) patients compared to healthy young and aged controls. We further characterise the endothelium as source of circulating Gal-9, which is increased in plasma of PAD patients compared to healthy controls. CONCLUSIONS: These results highlight a pathological role for Gal-9 as promoter of monocyte recruitment and atherosclerotic plaque progression, making it a novel target in the prevention of plaque formation and progression.

Characterisation of endogenous Galectin-1 and -9 expression in monocyte and macrophage subsets under resting and inflammatory conditions.

Macrophages are key cells in both acute and chronic inflammatory settings. Their activation and function highly depends on the cytokines, chemokines and adhesion molecules that direct monocytes to infiltrate tissues, differentiate into macrophages, and finally lead to the clearance of such inflammatory signals. Galectins, ß-galactoside-binding lectins, are differentially expressed by various immune cells, and some members of this family have been identified as regulators of leukocyte recruitment and activation. Galectin-1 (Gal-1) and galectin-9 (Gal-9) expression has been described in immune cells, but the specific molecular mechanisms by which they modulate the inflammatory response in macrophages/monocytes are not completely understood. In this study we sought to comprehensively characterise the expression profile of endogenous Gal-1 and Gal-9 in different murine and human monocyte/macrophage populations in response to different inflammatory stimuli. All subsets of murine and human macrophages expressed significant levels of Gal-1 and -9. Interestingly, murine bone marrow derived macrophages stimulated with M2 (pro-resolution) polarising agents preferentially upregulated Gal-1, while Gal-9 expression was upregulated by M1/pro-inflammatory stimulation. However, we observed differing results in human monocyte derived macrophages. Collectively, our findings report a differential expression pattern of endogenous Gal-1 and -9 in macrophage and monocyte subsets in response to a range of inflammatory stimuli. Future studies will endeavour to elucidate whether the galectins make attractive therapeutic targets or agents for regulating the inflammatory response.

In-depth immunophenotyping data relating to IL-17Ab modulation of circulating Treg/Th17 cells and of in situ infiltrated inflammatory monocytes in the onset of gouty inflammation.

The data supplied in this work are related to the research article entitled "IL-17A neutralizing antibody regulates monosodium urate crystal-induced gouty inflammation" [1]. This data article presents the results of the gating strategy applied to identify Treg population in peripheral blood of mice injected with MSU crystals and MSU crystals + interleukin-17 antibody (IL-17Ab). Lastly, this article provides in-depth immunophenotyping data relating to all specific and isotype control antibodies used in the phenotypical characterization of circulating Treg (defined as CD4+CD25+Foxp3+), Th17 (defined as CD4+IL-17+) cells and joint-infiltrated (in situ) inflammatory monocytes (defined as B220-GR1highF480highCD115+).