Mechanisms and Therapeutic Use of CR3 Signaling in Modulating Autoimmunity

描述（由申请人提供）：补体受体3（CR3）是在树突状细胞（DC）上发现的一种凋亡细胞受体，树突状细胞是免疫系统中最有效的抗原呈递细胞。我们证明了使用单克隆抗体激活DC上的CR3调节DC细胞因子表达并抑制其抗原呈递能力。CR3介导DC作用的确切机制尚不清楚，CR3连接的DC在体内诱导耐受的能力需要探索。 相关性：我们建议了解补体受体3介导的树突状细胞功能抑制的机制，并利用这些知识来治疗自身免疫。该提案旨在模仿生物制剂的成功，如利妥昔单抗或阿巴西普，这些生物制剂是从基础免疫学研究提供的知识中开发出来的。在这项建议中获得的经验将指导在风湿性疾病如MS和SLE的床边使用CR3介导的耐受性的努力。

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.