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Objective— UVB irradiation is an established treatment for immunoinflammatory cutaneous disorders and has been shown to suppress cutaneous and systemic inflammatory diseases through modulation of the adaptive immune response. However, it remains unknown whether UVB irradiation prevents an immunoinflammatory disease of arteries such as atherosclerosis. Approach and Results— Here, we show that UVB exposure inhibits the development and progression of atherosclerosis in atherosclerosis-prone mice by expanding and enhancing the functional capacity of CD4 + forkhead box P3 + regulatory T cells and regulating proatherogenic T-cell responses. Experimental studies in Langerhans cell–depleted mice revealed that epidermal Langerhans cells play a critical role in UVB-dependent induction of CD4 + forkhead box P3 + regulatory T cells, suppression of proatherogenic T-cell responses, and prevention of atherosclerotic plaque development. Conclusions— Our findings suggest the skin immune system as a novel therapeutic target for atherosclerosis and provide a novel strategy for the treatment and prevention of atherosclerosis.

Objective— Eicosapentaenoic acid (EPA) has been shown to have beneficial effects on cardiovascular diseases, although the precise mechanism is unknown. We investigated the effect of EPA on the regression of atherosclerosis. Methods and Results— LDL-receptor–deficient mice were fed a high-cholesterol diet for 8 weeks to build up aortic sinus atherosclerotic lesions and then were fed a normal diet with or without 5% EPA for 4 weeks. Atherosclerotic lesions were histologically assessed, and immunologic assays were performed. EPA treatment significantly regressed atherosclerosis (−22.7%, P + T cells, and dendritic cells (DCs) in atherosclerotic lesions, though only changing the chow never induced the regression. Flow cytometric analysis revealed that EPA increased immature DCs (CD11c + CD80 − CD86 − ), increased the indoleamine 2,3-dioxygenase (IDO) in DCs, and decreased the number of CD4 + T cells. In the presence of the IDO inhibitor, the beneficial effects of EPA on regression were inhibited, suggesting that the effect of EPA was mainly mediated through IDO. Conclusion— In addition to lowering plasma cholesterol, EPA regressed atherosclerosis probably due to modulation of DC phenotype and reduction in T cell numbers. The present findings might partly explain the beneficial effects of EPA in clinics and support clinical evidence.

Background Accumulating evidence suggests that the balance between pathogenic effector T cells (Teffs) and regulatory T cells (Tregs) may be important for controlling atherosclerotic disease. We hypothesized that a combination therapy with anti‐ CD 3 antibody ( CD 3‐Ab) and IL ‐2/anti‐ IL ‐2 monoclonal antibody complex ( IL ‐2 complex) aimed at increasing the ratio of Tregs to Teffs would effectively inhibit atherosclerosis in mice. Methods and Results We treated apolipoprotein E‐deficient mice fed a high‐cholesterol diet with vehicle, CD 3‐Ab, IL ‐2 complex, or their combination. Mice receiving the combination therapy had markedly reduced atherosclerotic lesions than mice treated with CD 3‐Ab or IL ‐2 complex alone. In addition, a striking increase in the Treg/Teff ratio of lymphoid organs and atherosclerotic lesions, along with plaque stabilization characterized by decreased macrophage content and increased collagen content was observed. The combination treatment also markedly reduced splenic Ly6C high inflammatory monocytes and might induce a favorable macrophage phenotype change in atherosclerotic lesions. Conclusions Our results indicate that in addition to suppressing Teff responses, enhancing Treg‐mediated immune responses is more efficacious in preventing atherosclerosis, suggesting a novel therapeutic approach for atherosclerosis.

Background: Reliable non-invasive imaging modalities to characterize atherosclerotic plaque components are clinically desirable for detecting unstable coronary plaques, which cause acute coronary syndrome or sudden death. Although recent clinical developments in computed tomography (CT) have enabled the visualization of luminal narrowing and calcified plaques in coronary arteries, the evaluation of non-calcified plaque components remains difficult. Phase-contrast X-ray CT imaging has great potential to reveal the structures inside soft tissues because its sensitivity to light elements is almost 1000 times greater than that of absorption-contrast clinical X-ray imaging. We for the first time examined mouse atherosclerotic plaques using phase-contrast X-ray CT and found promising results. Methods and Results: Ex vivo phase-contrast X-ray CT was performed using a synchrotron radiation source (SPring-8, Japan) to investigate atherosclerotic plaque components in mice. Samples were also histologically analyzed. Phase-contrast X-ray CT at a spatial resolution of 10 –20 μm revealed atherosclerotic plaque components, and thin fibrous caps could be easily detected. The specific mass densities of these components were estimated using dδ (differences in the refractive indexes relative to water). While lipid-rich areas showed low dδ (0.79 ± 0.13 × 10 −8 ) and mass density (1.011 ± 0.001 g/ml), the smooth muscle- and collagen-rich areas showed high dδ (4.18 ± 0.10 × 10 −8 and 5.93 ± 0.13 × 10 −8 , respectively) and mass density (1.057 ± 0.001 g/ml and 1.08 ± 0.002 g/ml, respectively). It was rather easy to evaluate or differentiate the atherosclerotic plaque components using this novel phase-contrast X-ray CT imaging. Moreover, the three-dimensional assessment of plaques was possible, and it enabled the imaging of their anatomical information. Conclusions: Phase-contrast X-ray CT can estimate the tissue-mass density of atherosclerotic plaques and distinguish the lipid-rich areas from the collagen-rich areas. This is a promising non-invasive technique for the investigation of plaque components and detection of unstable coronary plaques.