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.

Public Health 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08AI079396-01A1
Application #
7660579
Study Section
Allergy & Clinical Immunology-1 (AITC)
Program Officer
Prograis, Lawrence J
Project Start
2009-04-01
Project End
2014-03-31
Budget Start
2009-04-01
Budget End
2010-03-31
Support Year
1
Fiscal Year
2009
Total Cost
$133,920
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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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
Canna, Scott W; Wrobel, Julia; Chu, Niansheng et al. (2013) Interferon-? mediates anemia but is dispensable for fulminant toll-like receptor 9-induced macrophage activation syndrome and hemophagocytosis in mice. Arthritis Rheum 65:1764-75
Weaver, Lehn K; Behrens, Edward M (2013) How to use... antinuclear antibodies in paediatric rheumatic diseases. Arch Dis Child Educ Pract Ed 98:64-70
Canna, Scott W; Behrens, Edward M (2012) Not all hemophagocytes are created equally: appreciating the heterogeneity of the hemophagocytic syndromes. Curr Opin Rheumatol 24:113-8
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
Lerman, Ma; Burnham, Jm; Behrens, Em (2011) 1,25 dihydroxyvitamin D3 limits monocyte maturation in lupus sera. Lupus 20:749-53
Behrens, Edward M; Canna, Scott W; Slade, Katharine et al. (2011) Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice. J Clin Invest 121:2264-77