Role of group 2 innate lymphoid cells in knee ligament homeostasis during osteoarthritis

Osteoarthritis (OA) of the knee is a common condition that places a significant burden on society. Patients are treated for pain and by knee replacement at the end stage, as no disease modifying treatments are available. Ligaments play an important role in joint homeostasis by stabilizing the joint. Anterior cruciate ligament (ACL) injury is a frequent cause of secondary, post-traumatic knee OA affecting young patients. Degeneration of the ACL is also seen in primary OA. This project aims to address the role of failing ligament homeostasis in OA pathogenesis from an immunological perspective. Mechanical stress triggers an immune response, which in turn coordinates tissue repair. Tenocytes, the stromal cells of ligaments, sense forces applied to the ligament and produce immunostimulatory factors. Type 2 innate lymphoid cells (ILC2s) are found in most tissues and regulate tissue repair. Preliminary results from our lab suggest tenocytes can produce ILC2-activating factors and a population of ILC2 can be detected in tendons. A translational approach will be used to address the hypothesis that tenocyte-ILC2 cross talk is crucial in mediating ligament homeostasis. I will examine patient ACLs ex vivo and in vitro for factors of the tenocyte-ILC2 axis. I will then perform functional studies on these factors in a murine model of OA. Knowledge gained in this project can lead to the identification of novel therapeutic targets to promote ligament homeostasis and prevent OA progression.