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Regulatory T cells play an important role in the progression of atherosclerosis. GARP is a newly biological membrane molecule existed on activated Tregs, which is related to the release of TGF-β. The antiatherosclerosis effects of statins partly depend on their multiple immune modulatory potencies. In this paper, we present that atorvastatin could upregulate the expression of GARP and TGF-β in CD4+ T cells and increase the numbers of CD4+LAP+ and CD4+Foxp3+ regulatory T cells in ApoE−/− mice. Also, we indicate that atorvastatin promotes the aggregation of GARP+ and Foxp3+ cells and secretory of the TGF-β1 in atherosclerotic plaques. Furthermore, we prove that atorvastatin could delay the procession of atherosclerosis and improve the stability of atherosclerotic plaques. Interestingly, we report that inhibition of GARP distinctly inhibits the anti-inflammatory effects of atorvastatin. We conclude that atorvastatin improves the inflammatory response in atherosclerosis partly by upregulating the expression of GARP on regulatory T cells. [ABSTRACT FROM AUTHOR]

Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and affects ca. 10 million people worldwide. About 30% of Chagas disease patients develop chronic Chagas disease cardiomyopathy (CCC), a particularly lethal inflammatory cardiomyopathy that occurs decades after the initial infection, while most patients remain asymptomatic. Mortality rate is higher than that of noninflammatory cardiomyopathy. CCC heart lesions present a Th1 T-cell-rich myocarditis, with cardiomyocyte hypertrophy and prominent fibrosis. Data suggest that the myocarditis plays a major pathogenetic role in disease progression. Major unmet goals include the thorough understanding of disease pathogenesis and therapeutic targets and identification of prognostic genetic factors. Chagas disease thus remains a neglected disease, with no vaccines or antiparasitic drugs proven efficient in chronically infected adults, when most patients are diagnosed. Both familial aggregation of CCC cases and the fact that only 30%of infected patients develop CCC suggest there might be a genetic component to disease susceptibility.Moreover, previous case-control studies have identified some genes associated to human susceptibility to CCC. In this paper,wewill reviewthe immunopathogenesis and genetics of Chagas disease, highlighting studies that shed light on the differential progression of Chagas disease patients to CCC. [ABSTRACT FROM AUTHOR]

Statins are pharmacological inhibitors of the activity of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), an enzyme responsible for the synthesis of cholesterol. Some recent experimental studies have shown that besides their effects on the primary and secondary prevention of cardiovascular diseases, statins may also have beneficial anti-inflammatory effects through diverse mechanisms. On the other hand, the induction and activity of regulatory T cells (Treg) are key processes in the prevention of pathology during chronic inflammatory and autoimmune diseases. Hence, strategies oriented towards the therapeutic expansion of Tregs are gaining special attention among biomedical researchers. The potential effects of statins on the biology of Treg are of particular importance because of their eventual application as in vivo inducers of Treg in the treatment of multiple conditions. In this paper we review the experimental evidence pointing out to a potential effect of statins on the role of regulatory T cells in different conditions and discuss its potential clinical significance. [ABSTRACT FROM AUTHOR]

The skin is permanently exposed to physical, chemical, and biological aggression by the environment. In addition, acute and chronic inflammatory events taking place in the skin are accompanied by abnormal release of pro-oxidative mediators. In this paper, we will briefly overview the homeostatic systems active in the skin to maintain the redox balance and also to counteract abnormal oxidative stress. We will concentrate on the evidence that a local and/or systemic redox dysregulation accompanies the chronic inflammatory disorder events associated to psoriasis, contact dermatitis, and atopic dermatitis. We will also discuss the fact that several well-established treatments for the therapy of chronic inflammatory skin disorders are based on the application of strong physical or chemical oxidants onto the skin, indicating that, in selected conditions, a further increase of the oxidative imbalance may lead to a beneficial outcome. [ABSTRACT FROM AUTHOR]