IL-25 Inhibits Atherosclerosis Development in Apolipoprotein E Deficient Mice (original) (raw)
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Expansion of CD25 + Innate Lymphoid Cells Reduces Atherosclerosis
Arteriosclerosis, Thrombosis, and Vascular Biology, 2015
Objective— Innate lymphoid cells (ILCs) are a newly discovered subset of immune cells that promote tissue homeostasis and protect against pathogens. ILCs produce cytokines also produced by T lymphocytes that have been shown to affect atherosclerosis, but the influence of ILCs on atherosclerosis has not been explored. Approach and Results— We demonstrate that CD25 + ILCs that produce type 2 cytokines (ILC2s) are present in the aorta of atherosclerotic immunodeficient ldlr −/− rag1 −/− mice. To investigate the role of ILCs in atherosclerosis, ldlr −/− rag1 −/− mice were concurrently fed an atherogenic diet and treated with either ILC-depleting anti-CD90.2 antibodies or IL-2/anti-IL-2 complexes that expand CD25 + ILCs. Lesion development was not affected by anti-CD90.2 treatment, but was reduced in IL-2/anti–IL-2-treated mice. These IL-2-treated mice had reduced very low–density lipoprotein cholesterol and increased triglycerides compared with controls and reduced apolipoprotein B100 g...
BMC Immunology
Background Expansion of type 2 innate lymphoid cells (ILC2s) in hypercholesterolaemic mice protects against atherosclerosis while different ILC2 subsets have been described (natural, inflammatory) based on their suppression of tumorigenicity 2 (ST2) and killer-cell lectin like receptor G1 (KLRG1) expression. The aim of the current study is to characterize the interleukin 25 (IL25)-induced splenic ILC2 population (Lin−CD45+IL17RB+ICOS+IL7raintermediate) and address its direct role in experimental atherosclerosis by its adoptive transfer to hypercholesterolaemic apolipoprotein E deficient (apoE−/−) mice. Results Immunomagnetically enriched, FACS-sorted ILC2s from the spleens of IL-25 treated apoE−/− mice were stained for KLRG1 and ST2 directly upon cell obtainment or in vitro cell expansion for flow cytometric analysis. IL25-induced splenic ILC2s express high levels of both KLRG1 and ST2. However, both markers are downregulated upon in vitro cell expansion. In vitro expanded splenic I...
Lack of Interleukin1 Decreases the Severity of Atherosclerosis in ApoE-Deficient Mice
2010
Objective—Atherosclerosis is considered to be a chronic inflammatory disease and many cytokines participate in the development of atherosclerosis. We focused on the role of interleukin-1 (IL-1), one of the proinflammatory cytokines secreted by monocytes/macrophages, in the progression of atherosclerosis. Methods and Results—We generated mice lacking both apoE and IL-1. The sizes of atherosclerotic lesions at the aortic sinus in apoE//IL-1/mice
Changes in CD4(+)CD25(+) Tregs in the pathogenesis of atherosclerosis in ApoE(-/-) mice
Experimental biology and medicine (Maywood, N.J.), 2017
The goal of this study was to observe the pathological characteristics of atherosclerotic plaques in the aortic walls of ApoE(-/-) and C57BL/6J mice and the changes of CD4(+)CD25(+) regulatory T cells (Tregs) in atherosclerotic mice. Twenty ApoE(-/-) mice were split into high-fat diet (AH) and normal diet (AN) groups and 10 C57BL/6J male mice were designated as the control group (BN). The serum concentrations of IL-10 and TGF-β1 were detected by enzyme-linked immunosorbent assay; paraffin sections of the aorta were stained with hematoxylin & eosin, and morphometric parameters were measured using the Image Pro Plus 6.0 system. Verhoeff stain was used to observe the distribution of elastic fibers, and immunohistochemical staining was performed to verify the phenotype of the forkhead box protein 3 (Foxp3(+)) CD25(+) cells in the atherosclerotic tissue. The proportion of CD4(+)CD25(+) Tregs in the spleen was calculated by flow cytometry. The thickness of the intima, the intima/media rat...
Lack of Interleukin-1beta Decreases the Severity of Atherosclerosis in ApoE-Deficient Mice
Arteriosclerosis, Thrombosis, and Vascular Biology, 2003
Objective— Atherosclerosis is considered to be a chronic inflammatory disease and many cytokines participate in the development of atherosclerosis. We focused on the role of interleukin-1β (IL-1β), one of the proinflammatory cytokines secreted by monocytes/macrophages, in the progression of atherosclerosis. Methods and Results— We generated mice lacking both apoE and IL-1β. The sizes of atherosclerotic lesions at the aortic sinus in apoE−/−/IL-1β−/−mice at 12 and 24 weeks of age showed a significant decrease of approximately 30% compared with apoE−/−/IL-1β +/+ mice, and the percentage of the atherosclerotic area to total area of apoE−/−/IL-1β−/− at 24 weeks of age also showed a significant decrease of about 30% compared with apoE−/−/IL-1β +/+ . The mRNA levels of vascular cell adhesion molecule (VCAM)-1 and monocyte chemotactic protein-1 in the apoE−/−/IL-1β−/− aorta were significantly reduced compared with the apoE−/−/IL-1β +/+ . Furthermore, VCAM-1 was also reduced at the protein ...
Journal of Pathology, 2008
TNFα (TNF) critically regulates inflammation-driven atherosclerosis. Because the transmembrane (tmTNF) and soluble (sTNF) forms of TNF possess distinct immuno-modulatory properties, we hypothesized that they might differentially regulate atherosclerosis progression. Three groups of male ApoE−/− mice were studied: one expressing wild-type TNF (WT-TNF); one expressing exclusively a mutated non-cleavable form of TNF (KI-TNF); and one deficient in TNF (KO-TNF). Mice aged 5 weeks were fed the high-fat diet for 5 (T5) and 15 weeks (T15) or a standard chow diet for 15 weeks. At T5, in mice fed the high-fat diet, no significant differences in lesion area were observed among the three groups, either in valves or in aortas. At T15, lesion areas in valves were significantly lower in KO-TNF mice compared with those in WT-TNF mice, whereas in KI-TNF mice, they were intermediate between KO- and WT-TNF mice but not significantly different from these two groups. In aortas, lesions in KI-TNF were comparable to those of KO-TNF, both being significantly lower than those in WT-TNF. Theses differences were not linked to circulating lipids, or to macrophage, actin, and collagen contents of lesions. At T15, in mice fed the chow diet, lesion areas in valves and the aortic arch were not significantly different between the three groups. Levels of IL-6, IFNγ, IL-10, and Foxp3 mRNAs in spleens and production of IL-6, IL-10, MCP-1, RANTES, and TNFR-2 by peritoneal macrophages at T15 of the high-fat diet showed a decrease in pro-inflammatory status, more marked in KO-TNF than in KI-TNF mice. Apoptosis was reduced only in KO-TNF mice. In conclusion, these data show that TNF effects on atherosclerosis development are detectable at stages succeeding fatty streaks and that wild-type TNF is superior to tmTNF alone in promoting atherosclerosis. TNF-dependent progression of atherosclerosis is probably linked to the differential production of pro-inflammatory mediators whether tmTNF is preponderant or essentially cleaved. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.