REGULATION OF CHRONIC IMMUNE/INFLAMMATORY DISORDERS

本研究计划的目的是确定 调节异常炎症事件的分子机制 为了鉴定激动剂、拮抗剂和/或治疗剂的靶点， 干预致病条件。体外模型以及 实验动物系统，包括基因靶向模型（基因 基因敲除和转基因）和对以下疾病的遗传易感性模型 关节炎和其它慢性炎性疾病提供了 定义发病机制的机会。A组给药 链球菌细胞壁肽聚糖-多糖复合物 在遗传学上诱导关节炎、肝纤维化和脾细胞无反应性。 敏感的啮齿动物，并提供了一个模型，以探索所有阶段的一个 免疫反应及其失调的后果。在 此外，人类慢性炎性疾病的条件， 对外来植入物、传染性病原体或未知的反应 从细胞、分子和生物化学方面探讨了病因学 程度.这项研究的一个重要目标是确定已知的 以及在这些进化过程中表达的新分子 使人衰弱的炎性疾病。一种控制机制 这些病理事件是通过口服耐受和诱导 TGF-β此外，还应规范 炎症和组织破坏 靶向基因治疗可能为发病机制提供新的见解 和治疗干预。

The objective of this research program is to define molecular mechanisms that regulate aberrant inflammatory events to identify targets for agonists, antagonists and/or therapeutic intervention in pathogenic conditions. In vitro models and experimental animal systems including gene targeting models (gene knockouts and transgenics) and models of genetic susceptibility to arthritis and other chronic inflammatory diseases provide opportunities to define pathogenesis. Administration of group A streptococcal cell wall peptidoglycan-polysaccharide complexes induces arthritis, liver fibrosis, and spleen cell anergy in genetically susceptible rodents and provides a model to explore all phases of an immune response and the consequences of its dysregulation. In addition, human conditions of chronic inflammatory disease in response to foreign implants, infectious pathogens or of unknown etiology are explored at the cellular, molecular and biochemical levels. An important objective of this research is to identify known and novel molecules expressed during the evolution of these debilitating inflammatory diseases. One mechanism for controlling these pathologic events is through oral tolerance and the induction of TGF-beta. In addition, regulation of the processes of inflammation and tissue destruction by both local and systemically targeted gene therapy may provide new insight into pathogenesis and therapeutic intervention.