Role of nucleosome-induced neutrophil activation in systemic lupus erythematosus

• Applicant: Dr. Patrice Decker
• Subject Area: Immunology
• Term: from 2003 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5413084

Systemic lupus erythematosus (SLE) is a rheumatic autoimmune disease characterized by the production of autoantibodies (autoAb) directed mostly against nuclear autoantigens (autoAg). The nucleosome is a major autoAg since autoreactive nucleosome-specific B and T lymphocytes have been found in lupus patients. Moreover, circulating nucleosomes are detected in patient sera and the levels of circulating nucleosomes and anti-nucleosome autoAb are correlated to disease activity. SLE is also characterized by its inflammation state. Neutrophils are the first cells recruited at inflammation sites where they are activated. Interestingly, previous studies have shown that lupus sera contain a neutrophil-activating agent. Moreover, nucleosomes were found to deposit at inflammation sites in patients. Most importantly, it has been suggested that neutrophils may link innate and adaptive immunity. Since nucleosomes were already shown to bind and act on diverse cells, we want to test whether nucleosomes could bind and activate human normal and lupus neutrophils ex vivo and whether they are able to recruit and activate neutrophils in vivo. Moreover, we plan to test whether this results in activation of other cells, particularly dendritic cells and lymphocytes in order to link the presence of circulating nucleosomes to inflammation state and specific immunity in SLE patients.

• DFG Programme: Research Grants