Mechanisms and Therapeutic Use of CR3 Signaling in Modulating Autoimmunity

描述(申请人提供)：补体受体3(CR3)是一种发现于树突状细胞(DC)上的凋亡细胞受体，树突状细胞(DC)是免疫系统最强大的抗原提呈细胞。我们证明了用单抗激活树突状细胞表面的CR3可以调节树突状细胞细胞因子的表达并抑制其抗原提呈能力。CR3介导树突状细胞作用的确切机制尚不清楚，其体内诱导耐受的能力有待进一步研究。 相关性：我们建议学习补体受体3介导的抑制树突状细胞功能的机制，并利用这一知识来治疗自身免疫。这项提议旨在效仿生物学的成功，如利妥昔单抗或阿巴坦普，这些生物学是从基础免疫学研究提供的知识发展而来的。从这项提案中获得的经验将指导人们在风湿性疾病(如MS和SLE)的床边使用CR3介导的耐受。

DESCRIPTION (provided by applicant): Complement Receptor 3 (CR3) is an apoptotic cell receptor found on dendritic cells (DCs), the most potent antigen presenting cell of the immune system. We demonstrated that activation of CR3 on DCs using a monoclonal antibody modulates DC cytokine expression and inhibits their antigen presentation capacity. The exact mechanism through which CR3 mediates its effects of DCs is still unknown, and the ability of CR3 ligated DCs to induce tolerance in vivo needs exploration. RELEVANCE: We propose to learn the mechanisms of Complement Receptor 3 mediated suppression of dendritic cells function, and to harness this knowledge to treat autoimmunity. This proposal aims to emulate the success of the biologies, such as Rituximab or Abatacept, that were developed from the knowledge provided by basic immunology research. The experience gained in this proposal will direct efforts toward using CR3 mediated tolerance at the bedside in rheumatic diseases such as MS and SLE.