Functional specialization of Foxp3+ regulatory T cells

免疫介导的自身免疫性疾病和炎性疾病是一个主要的公共卫生问题。限定 因此，通常起预防肺部炎症作用的调节机制是关键 了解这些疾病的病因，并制定治疗策略，以提高 这些活动在患者。表达转录因子Foxp 3的调节性T细胞（TR）发挥着重要作用。 在预防自身免疫和限制免疫介导的炎症中起关键作用。我们已经表明 在1型炎症反应中，Foxp 3 + TR上调Th 1特异性转录， 因子Tbx 21（T-bet），并且T-bet表达对于适当的TR稳态和功能至关重要 Th 1介导的炎症。因此，本提案的目标是详细确定 Foxp 3 + TR内T-bet特异性缺失如何影响 体内Th 1应答（特异性目的1）;在分子水平上分析Foxp 3和T-bet如何结合联合收割机 控制参与Th 1/TR分化、稳态和功能的基因的表达 （具体目标2）;以及鉴定控制表型和细胞周期的细胞因子和细胞信号。 不同TR亚群的功能分化（具体目标3）。

Immune-mediated autoimmune and inflammatory diseases are a major public health issue. Defining the regulatory mechanisms that normally function to prevent pulmonary inflammation is therefore key to understanding the etiology of these diseases, and for developing therapeutic strategies to boost these activities in patients. Regulatory T cells (TR) expressing the transcription factor Foxp3 play a critical role in preventing autoimmunity and limiting immune-mediated inflammation. We have shown that during type-1 inflammatory responses, Foxp3+ TR upregulate the Th1-specifying transcription factor Tbx21 (T-bet), and that T-bet expression is critical for proper TR homeostasis and function during Th1-mediated inflammation. Therefore, the goals of this proposal are to determine in detail how loss of T-bet specifically within Foxp3+ TR impacts the initiation, progression and termination of Th1 responses in vivo (Specific Aim 1); analyze at the molecular level how Foxp3 and T-bet combine to control the expression of genes involved in Th1/TR differentiation, homeostasis and function (Specific Aim 2); and to identify the cytokines and cellular signals that control the phenotypic and functional differentiation of different TR subsets (Specific Aim 3).