Abstract 10854: Activation of Regulatory T Cells by Ultraviolet Irradiation Controls Atherogenesis in Mice
Background: Epidemiological studies have reported higher rates of coronary heart disease with increasing altitude of residence, which might be attributed to less exposure to sunlight including ultraviolet B (UVB). Numerous studies have demonstrated that UVB irradiation induces immunosuppression. We hypothesized that low-dose UVB irradiation to the skin would inhibit atherosclerosis via suppression of pathogenic immune responses in mice.
Methods and Results:Six-week-old apolipoprotein E-deficient (ApoE-/-) mice (n=10 per group) were UVB irradiated (5kJ/m2) once a week and atherosclerosis was assessed at 20 weeks old. UVB irradiation significantly reduced atherosclerosis development (aortic sinus plaque area: 1.84±0.20×105 vs. 2.94±0.31×105 μ m2, p<0.01) compared to controls, as well as decreased macrophage content by 41% and CD4+ T cell infiltration by 39% in the lesions, and inhibited the progression of established lesions. Six-week-old 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 for 4 weeks. UVB irradiation (5kJ/m2, twice per week) significantly decreased lipid content of the plaques (-40%, p<0.05, n=8), whereas only changing the diet (n=8) did not. UVB-irradiated mice showed a marked increase in both CD4+ effector T cells and Foxp3+ regulatory T cells (Tregs) exhibiting activated phenotype and potent suppressor function, along with suppressed T-helper type 1 immune responses, implying that UVB-induced Tregs might control over effector T-cell immune responses. Depletion of Foxp3+ Tregs in hyperlipidemic foxp3-diphtheria toxin receptor/ApoE-/- transgenic mice resulted in rather augmented effector T-cell immune responses and abrogated the athero-protective effect by UVB treatment, arguing for a critical role of UVB-induced Foxp3+ Tregs in the down-regulation of immune responses and reduction of atherosclerosis.
Conclusions: Low-dose UVB irradiation to the skin reduces atherosclerosis and lipid content of the established plaques through the induction of activated Tregs. Immune modulation through the skin may represent an attractive therapeutic approach to atherosclerosis.
- © 2012 by American Heart Association, Inc.