Angelo A. Manfredi

Research activities

1. Molecular control of persistent vascular inflammation in systemic vasculitis and systemic autoimmune diseases. Vessel walls inflammation has dramatic consequences. The initiating or precipitating event is often unknown, and a self-sustaining circuit attracts and activates inflammatory leukocytes in the wall of vessels. We are studying the role of injury-associated signals and acute phase proteins on the activation of circulating leukocytes, platelets and endothelial cells in the pathogenesis of systemic vasculitis and in the extrarticular manifestations of patients with rheumatoid arthritis.
2. In vivo outcomes of massive cell death induced by anti-neoplastic treatments. Massive cell death elicited by antineoplastic treatments, such as neo-adjuvant radio-chemotherapy in patients with colorectal cancer, correlates with divergent clinical outomes. We are actively investigating the molecular basis of the heterogeneous response to tumor cell death, in order to identify the relevant molecular events that control tumor immunogenicity in neoplastic patients, with attention to the involvement of Toll like receptors and other innate receptors responsible for the inflammatory response to cell injury.
3. Cross presentation of antigens originated during cell death and the origin of autoimmune responses. Generation/release of autoantigens and of homeostatic inflammatory signals characterize tissue injury. Activated dendritic cells (DCs) as a consequence migrate to secondary lymphoid organs and upregulate the molecular machinery required for the priming of naive T cells, including T lymphocytes recognizing autoantigens. We are veryfing in various models of systemic autoimmunity (systemic lupus erythematosus, autoimmune myositis) the possibility that cues generated at sites of injury shape T-cell clonal expansion, regulating sensitivity to activation-dependent apoptosis and commitment towards polarized T-cell fates.

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