Human and experimental animal studies to identify mechanisms governing lymph transport in Crohn’s disease.

Lymphatic vessels are specialized vessels that transport immune cells and fat out of the gut to maintain health. Surgeons treating Crohn’s disease decades ago argued that impaired lymphatic flow may be a key problem in the disease. However, only recently have tools emerged to study lymphatic vessels in detail. We have data that lymph transport is impaired even in early Crohn’s disease. However, treatments targeting the cytokine TNF reverse the impaired transport. As investigators specializing in different lymphatic research areas, we will synergistically utilize human subjects’ studies with research in mice and rats to map in detail how terminal ileal inflammation alters lymph flow. We will also address whether a gut hormone called GIP that is overproduced in the setting of TNF neutralizing therapy accounts for how therapy against TNF restores lymph flow. If so, mimetics of the hormone may have utility in subjects unable to use therapeutics against TNF.