Mechanisms and Therapeutic Use of CR3 Signaling in Modulating Autoimmunity

补体受体3 （CR3）是一种在树突状细胞（dc）上发现的凋亡细胞受体，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可以调节DC细胞因子的表达并抑制其抗原递呈能力。CR3介导其对dc的作用的确切机制尚不清楚，CR3连接dc诱导体内耐受的能力有待探索。

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.