Neutrophils are short-lived innate leukocytes that modulate inflammation and immune responses. They are rapidly recruited to sites of tissue injury where they perform diverse and essential functions, including phagocytosis, release of potent molecules with antibacterial properties from their granules, and the extrusion of neutrophil extracellular traps (NETs) in a process called NETosis.
“Recent evidence implicates neutrophil dysregulation in the pathogenesis of various systemic autoimmune diseases and associated organ damage,” said Mariana Kaplan, MD, Senior Investigator and Chief of the Systemic Autoimmunity Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, Bethesda, MD. “These discoveries highlight neutrophils as putative targets for therapeutic modulation in systemic autoimmunity.”
Dr. Kaplan will discuss the role of neutrophils in autoimmune disease and in cardiovascular pathogenesis during the session, Immunology Update: Neutrophils, Multi-Armed Primitive Warriors, on Monday, from 7:30 – 8:30 am in Room B309.
Dr. Kaplan’s research at NIAMS has focused on identifying mechanisms of organ damage and premature vascular disease in systemic autoimmunity. More specifically, she investigates how innate immunity (in particular, type I interferons and myeloid cells) promote end-organ damage in systemic lupus erythematosus, rheumatoid arthritis, and other systemic autoimmune diseases. Recently, her research has focused on identifying abnormalities of neutrophil subsets and the role of neutrophil extracellular traps in lupus and rheumatoid arthritis, both of which may contribute to the development of autoimmune responses and end-organ damage.
Dr. Kaplan also has an interest in identifying novel therapeutic targets that may prevent premature vascular damage in systemic autoimmunity, as well as the role of environmental triggers in the induction of autoimmunity. Moreover, she has led clinical trials to identify mechanisms that reduce blood vessel dysfunction in autoimmune and chronic inflammatory disorders.
“Research has demonstrated that neutrophils are more heterogeneous than previously thought and that certain neutrophil subsets have distinct pathogenic features in autoimmune diseases,” Dr. Kaplan said. “Additionally, dysregulation in NET formation and clearance contributes to the pathogenesis of autoimmune and autoinflammatory syndromes.”
Neutrophil heterogeneity and distinct pathogenic subsets, she said, contribute to the pathogenesis of diseases such as lupus, rheumatoid arthritis, systemic vasculitis, crystal-deposition diseases, and autoinflammatory syndromes.
“The roles of neutrophils in these diseases include initiation and propagation of autoimmune responses, tissue damage and premature vascular disease,” Dr. Kaplan said. “Drugs that target aberrant neutrophil phenotype and function may play an important role in the treatment of certain rheumatic conditions.”