dr caroline jefferies

Researchers on the Path to a Cure – Spotlight on Dr. Caroline Jefferies

Lupus is a chronic, autoimmune disease and affects a wide part of the body, including the joints, kidneys, skin, blood, brain and other organs. One of our six Delivering on Discovery projects focuses on Lupus and lung disease. “Lupus is a complex disease. It affects many organs. The number of lupus patients with lung inflammation is probably underestimated. Yet it negatively impacts the quality of life in these patients,” explained Dr. Caroline Jefferies. “And while we have a basic understanding about how lupus affects various organs, we need to better understand how it affects the lungs to better manage and treat it.”

Dr. Jefferies is focusing on the lungs with her 3-year Arthritis Foundation-funded project, “Inflammatory neutrophils in lupus lung disease –  novel cellular target”.

Neutrophils are a type of white blood cell found in the immune system. They contain granules with enzymes that are released during infections and allergic reactions. During an immune response, neutrophils release some of their DNA in the form of neutrophil extracellular traps (NETs), which allow them to kill pathogens and minimize damage to cells.

When neutrophils are inappropriately activated, NETs drive inflammation and can contribute to tissue damage. Recently, NETs have been shown to be strongly involved in lupus heart and kidney disease. In terms of lung disease, NETs have been identified as playing a role in cystic fibrosis, as well as acute lung injury and infection patients.

Another factor the team is looking into is endoplasmic reticulum (ER) stress. The ER is a part of the cell that is involved in the construction of protein molecules and the transport of newly made proteins to other parts of the cell. ER stress can lead to the release of inflammatory molecules (cytokines) that attract cells to the damaged area and cause lung tissue structure to be changed. Dr. Jefferies is investigating whether ER stress can drive neutrophil activation and in this may drive autoimmune lung disease.

Dr. Jefferies and her team are trying to more fully understand the role of neutrophils and ER stress in lung injury caused by the immune system – first using mice, and in later stages of this study using human cell cultures. The team has been working on this project since April and expect to see results from the early mouse studies in early 2018.

Not long after coming to the U.S. from Dublin, Ireland in 2015, Dr. Jefferies and her team applied for the foundation’s Delivering on Discovery grant. She feels that the Arthritis Foundation’s mission and her personal goals are closely aligned. She is doing research that focuses on translation of research – creating a cure for patients. “When you have an autoimmune disease like lupus, your immune system constantly attacks your body, making it feel like you are always fighting a virus. But it’s not,” explained Dr. Jefferies. “We’re trying to figure out how to reset the immune system so that it stops attacking itself. This research will have applications to many autoimmune diseases, including many forms of arthritis – not just lupus.”

Dr. Jefferies is an associate professor/researcher with the Cedars-Sinai Medical Center Division of Rheumatology in Los Angeles, CA.

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