From Vanilla to 28 Flavors: Multiple Varieties of T Regulatory Cells
ABSTRACT Numerous T cell subpopulations have now been claimed to exhibit regulatory activity. Shevach discusses the current understanding of the different subsets of T regulatory cells and provides a perspective on the current areas of uncertainly and controversy in the field.
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ABSTRACT: The underlying mechanism of ischemic stroke is not completely known. Regulatory T cells (Tregs), a subset of T cells, play a pivotal role in the pathophysiological process of ischemic stroke. However, there is also controversy over the role of Tregs in stroke. Hence, the function of Tregs in ischemic stroke has triggered a heated discussion recently. In this paper, we reviewed the current lines of evidence to describe the full view of Tregs in stroke. We would like to introduce the basic concepts of Tregs and then discuss their paradox function in ischemic stroke. On one side, Tregs could protect brain against ischemic injury via modulating the inflammation process. On the other side, they exaggerated the insult by causing microvascular dysfunction. They also interfered with the neurological function recovery. In addition, the reasons for this paradox role would be discussed in the review and the prospective of the clinical application of Tregs was also included. In conclusion, Tregs contributed to the outcome of ischemic stroke, while more lines of evidence are needed to understand how Tregs regulate the immune system and influence the outcome of stroke.The Scientific World Journal 10/2013; 2013:174373. DOI:10.1155/2013/174373 · 1.73 Impact Factor
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ABSTRACT: Beneficial effects of non-pathogenic bacteria are increasingly recognized. We reported in a placebo-controlled study with atopic dermatitis (AD) patients that cutaneous exposure to lysates of non-pathogenic bacteria alleviates skin inflammation. To now unravel underlying mechanisms, immune consequences of sensing non-pathogenic bacterium Vitreoscilla filiformis lysate (Vf) were characterized analyzing (i) differentiation of dendritic cells (DC) and, consecutively, (ii) effector functions of DC and Th cells in vitro and in a murine model of AD in NC/Nga mice in vivo. Topical treatment with Vf significantly reduced AD-like inflammation in NC/Nga mice. Importantly, cutaneous exposure to Vf in combination with the allergen FITC significantly reduced also subsequent allergen-induced dermatitis indicating active immune modulation. Indeed, innate sensing of Vf predominantly induced IL-10 producing DC, which was dependent on TLR2-activation. Vf-induced IL-10+ DC primed naïve CD4+ T helper cells to become regulatory IFN-γ(low) IL-10(high) Tr1 cells. These IL-10(high) Tr1 cells were also induced by Vf in vivo and strongly suppressed T effector cells and inflammation. In conclusion we show that innate sensing of non-pathogenic bacteria by TLR2 induces tolerogenic DC and regulatory Tr1 cells suppressing T effector cells and cutaneous inflammation. These findings indicate a promising therapeutic strategy for inflammatory skin diseases like AD.Journal of Investigative Dermatology accepted article preview online, 28 June 2013; doi:10.1038/jid.2013.291.Journal of Investigative Dermatology 06/2013; DOI:10.1038/jid.2013.291 · 6.37 Impact Factor
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ABSTRACT: Osteoimmunology is the crosstalk between the skeletal and immune system. We have previously shown in vitro that osteoclasts (OC) crosspresent antigens to induce FoxP3 in CD8 T-cells (OC-iTcREG), which then suppress osteoclast activity. Here we assessed the ability of OC-iTcREG to limit bone resorption in vivo. Mice lacking CD8 T-cells lose more bone in response to RANKL (Tnfsf11) administration. Using adoptive transfer experiments we demonstrate that FoxP3(+) CD8 T-cells limit bone loss by RANKL administration. In ovariectomized mice, a murine model of postmenopausal osteoporosis, OC-iTcREG limited bone loss and increased bone density as assessed by serum markers, micro computed tomography (μCT) and histomorphometry. Indeed, OC-iTcREG-treated ovariectomized mice had decreased levels of effector T-cells in the bone marrow compared to untreated mice, and increased bone formation rates relative to bisphosphonate-treated mice. Our results provide the first in vivo evidence that OC-iTcREG have anti-resorptive activity and repress the immune system, thus extending the purview of osteoimmunology.Bone 06/2013; 56(1). DOI:10.1016/j.bone.2013.05.024 · 4.46 Impact Factor