The branch is focusing on identifying the role of aberrant neutrophils and neutrophil extracellular traps in the development of autoimmune responses and end-organ damage in systemic diseases including lupus (SLE), rheumatoid arthritis (RA), inflammatory myopathies and systemic vasculitides (AAV) and autoinflammatory syndromes. We are also examining how sex differences contribute to neutrophil biology. During this year, our group reported how lupus neutrophils modulate T cell function and mechanisms of oxidant production by neutrophils that may promote immune-mediated damage in lupus and other diseases. Our group also reported the association between low density granulocytes and coronary artery disease and vascular inflammation in a cohort of lupus patients. Our work is also examining neutrophil heterogeneity in humans to understand how specific subsets may modulate health and disease. Other areas of interest to our group pertaining to the role of neutrophils in autoimmunity relate to inflammatory myopathies and systemic vasculitis, and their role in various auto inflammatory syndromes including PAPA and DADA2. Recent collaborative work has focused on further understanding dysregulation in mitochondrial pathways in SLE as well as the role of the immunoproteasome in this disease. We continue to use sophisticated imaging and functional vascular assays to quantify blood vessel abnormalities in lupus patients. We have an ongoing clinical trial to assess the role of PPAR-gamma agonists in modulating vascular function and disease activity in lupus patients, at the NIH Clinical Center and recently completed a trial not he role of JAK inhibitors in SLE that included vascular outcomes. An ongoing trial on the role of exercise in SLE is also including vascular trials. How lipoprotein dysregulation contributes to lupus vascular disease is an area of current work in the lab. The branch uses sophisticated gene expression approaches including RNA sequencing, ATAC sequencing and single cell RNA sequencing to better understand cellular heterogeneity in autoimmune diseases and the role of specific cell subsets in mediating pathogenesis.

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Budget End
Support Year
6
Fiscal Year
2019
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Indirect Cost
Name
National Institute of Arthritis and Musculoskeletal and Skin Diseases
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Demoruelle, M Kristen; Bowers, Emily; Lahey, Lauren J et al. (2018) Antibody Responses to Citrullinated and Noncitrullinated Antigens in the Sputum of Subjects With Rheumatoid Arthritis and Subjects at Risk for Development of Rheumatoid Arthritis. Arthritis Rheumatol 70:516-527
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