NETs

Neutrophils are a type of white blood cell that can help fight infections. They also contribute to inflammation, which can be helpful when the body is fighting an infection. Neutrophils sometimes cause inflammation even when there is no infection, like in RA. Neutrophils are the predominant white blood cell found in the joints of patients with RA where they contribute to joint inflammation. Understanding exactly how neutrophils contribute to inflammation in RA could help to identify new ways to treat and prevent RA.

 

Studies have found that neutrophils in the blood and joint fluid of patients with RA are more prone to neutrophil extracellular trap (NET) formation (also called NETosis). NET formation is a process during which neutrophils decondense their cell nucleus and extrude their nuclear contents into net-like structures. NETs are helpful in fighting infection, but when neutrophils undergo NETosis in RA, they cause inflammation and tissue damage. In RA, neutrophils undergo excessive NET formation that leads to damaging inflammation.

 

Our team’s work in this area has made several important findings. We found that neutrophils from the lungs in patients with RA and individuals at increased risk of developing RA are more prone to undergo NETosis. This increased NET formation in the lungs was also associated with increased lung inflammation. Our findings also found that NET-bound proteins can contribute to autoantibody production in the lungs in individuals at increased risk of developing RA. These findings have contributed to the field’s improved understanding of how NETosis contributes to RA pathogenesis.

 

Our ongoing work in this area continues to unravel the role of NETosis in RA. In particular, we are investigating which triggers and signaling pathways contribute to the higher rates of NET formation in patients with RA and individuals at-risk of RA. We are also studying whether clearance of NETs in the lung is reduced or inadequate in RA, which could also lead to higher levels of NET proteins. Ultimately, we hope to determine whether therapies targeting NETosis in the lung could improve the treatment of RA and potentially prevent RA in those who are at increased risk.