Studies of neutrophils in autoimmune joint inflammation

Neutrophils are the most abundant cells found in inflamed joints of patients with rheumatoid arthritis (RA), and animal models identify a central role for neutrophils in autoimmune joint inflammation.

Despite this, we have a limited understanding of how neutrophils are regulated in human disease, and no precision drugs affecting neutrophils exist.The lack of understanding related to neutrophils can be attributed to the difficulty of studying them.

To overcome this, my group has developed unique model systems enabling detailed molecular studies of neutrophils in different relevant in vitro and in vivo settings.The purpose of the presented studies is to (i) investigate molecular mechanisms responsible for neutrophil migration and activation in RA patients, and (ii) systematically identify and prioritize drug targets that affect these neutrophil behaviors.We will perform a PET study to track neutrophil dynamics in RA patients, use patient synovial fluid to identify factors responsible for neutrophil migration towards the inflamed joint, and use our established CRISPR platform to identify how neutrophil migration and activation can be suppressed.

These studies will be followed by efforts to identify biomarkers that can stratify patients based on neutrophil phenotypes.This research is important as it addresses an understudied topic of clinical relevance, aiming to develop novel precision drugs and related biomarkers for patients with neutrophil-mediated pathology.