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.
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.
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|Weaver, Lehn K; Behrens, Edward M (2014) Hyperinflammation, rather than hemophagocytosis, is the common link between macrophage activation syndrome and hemophagocytic lymphohistiocytosis. Curr Opin Rheumatol 26:562-9|
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|Canna, Scott W; Behrens, Edward M (2012) Making sense of the cytokine storm: a conceptual framework for understanding, diagnosing, and treating hemophagocytic syndromes. Pediatr Clin North Am 59:329-44|
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