Investigating the Requirement for Tbet Expression during Psoriasis

十多年来，一些慢性炎症性疾病，包括多发性硬化症，类风湿 关节炎和银屑病被描述为Th1介导的疾病，因为产生IFNy的CD4T细胞 在疾病患者中普遍存在，IFNy强烈激活巨噬细胞，增强炎症。 然而，大量自身免疫性/慢性炎症性疾病动物模型的最新数据表明 Th17效应者CD4T细胞是疾病的诱因。有趣的是，这些疾病的发生 慢性炎症性疾病与IFNY+和IL-17+效应细胞CD4T的升高有关 炎症部位的细胞，开启了关于这些效应者CD4T细胞单独作用的辩论 疾病期间的人口。事实上，Th1CD4T细胞对银屑病发展的影响仍然存在 不清楚。在某些实验条件下，IL-12刺激可以诱发银屑病，而这 病理与IFNY水平升高有关，尽管已证明IFNY与此无关 对于驱使疾病是必不可少的。Th1相关转录因子Tbet和STAT4需要诱导 一些慢性炎症的实验模型，如EAE和结肠炎，即使IFNY不是。至 迄今为止，人们对这些转录调节因子在牛皮癣发展过程中的作用知之甚少。 我们假设Tbet和STAT4，Th1相关的转录因子，是Th1相关的转录因子 CD4T细胞介导的银屑病的发生发展我们提出了以下具体目标来确定 Tbet和STAT4在两种不同效应机制的银屑病模型中的作用。 目的1.银屑病的发生发展需要Tbet。 目的：STAT4信号转导通路在银屑病发病中起关键作用。 总而言之，这些研究旨在提供关于心力衰竭的分子机制的新信息。 CD4T细胞介导的银屑病。这些研究的发现可能会确定新的潜在目标 旨在消除牛皮癣以及其他慢性炎症性疾病的治疗和/或预防策略 精神错乱。

For over a decade, a number of chronic inflammatory disorders including multiple sclerosis, rheumatoid arthritis, and psoriasis have been described as Th1 -mediated disorders because IFNy-producing CD4 T cells are prevalent in diseased patients and IFNy strongly activates macrophages, potentiating inflammation. However recent data from animal models of numerous autoimmune/chronic inflammatory disorders suggests that Th17 effector CD4 T cells are responsible for the induction of disease. Interestingly, the onset of these chronic inflammatory diseases is associated with elevated numbers of both IFNy+ and IL-17+ effector CD4 T cells at the sites of inflammation, opening the debate on the individual roles of these effector CD4 T cell populations during disease. In fact, the impact of Th1 CD4 T cells on the development of psoriasis remains unclear. Under certain experimental conditions, psoriasis can be induced by IL-12 stimulation and this pathology is associated with increased levels of IFNy, although it has been demonstrated that IFNy is not essential to drive disease. The Th1-associated transcription factors Tbet and STAT4 are required to induce some experimental models of chronic inflammation, such as EAE and colitis, even when IFNy is not. To date, little is known about the role of these transcriptional regulators during the development of psoriasis. We hypothesize that Tbet and STAT4, Th1-associated transcription factors, are necessary for the development of psoriasis mediated by CD4 T cells. We propose the following specific aims to determine the role of Tbet and STAT4 during two models of psoriasis mediated by distinct effector mechanisms. Aim 1. Tbet is required for the development of psoriasis. Aim 2. STAT4 signaling is critical for the onset of psoriasis. Collectively, these studies are designed to provide new information regarding the molecular mechanisms of CD4 T cell-mediated psoriasis. The findings from these studies may identify new potential targets for therapeutic and/or preventative strategies designed to ablate psoriasis, as well as other chronic inflammatory disorders.