BME PhD Proposal Seminar: Echoe M. Bouta

Targeting Lymphatics to Ameliorate Joint Inflammation in a Mouse Model of Rheumatoid Arthritis

Supervised by Dr. Edward Schwarz

Abstract:

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with episodic flares. In TNF-Tg mice, a model of inflammatory-erosive arthritis, the popliteal lymph node (PLN) expands during the pre-arthritic expanding phase and then “collapses” during flare. This PLN collapse is also associated with decreased lymphatic transport, which is hypothesized to be responsible for insufficient clearing of inflammatory cytokines and cells in the joint space, leading to joint destruction. Currently, the factors that cause PLN collapse are unknown. Local changes in physiology are reasonable explanations given the finding that PLN and iliac lymph node collapse occurs in series along the ipsilateral axis in the setting of unaltered chronic inflammation and systemic autoimmunity.

Additionally, it has been reported that between the expanding and collapsed phases, there is no significant change in volume. Therefore, we move to redefine the two phases associated with pre-flare and flare as “Draining” and “Clogged”, respectively, due to the condition of the sinuses. These two phases will be phenotyped by lymph node contrast enhancement, a method to measure lymph node uptake. Also, we aim to determine if arthritic flare is dependent on lymphatic pressure, lymph viscosity and/or blood flow within the PLN using novel methods. Furthermore, it is hypothesized that these parameters and lymphatic transport can be targeted by drugs to ameliorate inflammatory arthritis in TNF-Tg mice, due to the fact that lymphatic transport is hindered during lymph node collapse (flare).

Therefore, our central hypothesis is that arthritic flare secondary to the clogging of the efferent lymph node is triggered within the lymphatic system, and can be treated by increasing lymphatic transport.