REGULATION OF CHRONIC IMMUNE/INFLAMMATORY DISORDERS

这项研究计划的目标是确定 调控异常炎症事件的分子机制 确定激动剂、拮抗剂和/或治疗药物的靶点 对致病条件的干预。体外模型和 实验动物系统，包括基因打靶模型(基因 基因敲除和转基因)和遗传易感性模型 关节炎和其他慢性炎症性疾病提供 定义发病机制的机会。A组的管理 链球菌胞壁肽聚糖-多糖复合体 遗传性关节炎、肝纤维化和脾细胞无能 并提供了一种模型来探索 免疫反应及其失调的后果。在……里面 此外，慢性炎症性疾病的人类状况 对外来植入物、感染性病原体或不明原因的反应 病因学从细胞、分子和生化方面进行了探讨。 级别。这项研究的一个重要目标是识别已知的 以及在这些进化过程中表达的新分子 衰弱的炎症性疾病。一种控制的机制 这些病理事件是通过口服耐受和诱导 转化生长因子-β。此外，对过程的监管 局部和全身炎症和组织破坏 靶向基因治疗可能为发病机制提供新的见解 和治疗性干预。

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.