Research Group
- Dr Lorna Marson, Principal Investigator
- Dr Jeremy Hughes, Co-Investigator
Location
- Queen’s Medical Research Institute, Edinburgh, UK
Title
- Mechanistic Studies of Lymphangiogenesis in Kidney Transplantation and Its Role in Immune Injury
One of the greatest challenges in renal transplantation is chronic allograft injury (CAI), characterised by tubular atrophy and interstitial fibrosis. The focus of much research has been the modulation of T cell-mediated injury, but this has not significantly altered the course of CAI. We have focused on the lymphatic system as a potentially exciting therapeutic target.
At the time of transplantation, lymphatic vessels are divided, with no attempt to reconnect them. It is clear that reconnection does occur; the alloimmune response is dependent on lymphocyte trafficking to and from draining lymph nodes.
We have studied the process of lymphatic reconnection in a rodent model and have demonstrated that this occurs by day 6; the new lymphatics form a mesh of new vessels, distinct from the original lymphatic trunks.
We have developed a murine model of CAI characterised by tubular atrophy and interstitial fibrosis over 8 weeks. We have demonstrated a significant increase in the number of lymphatic vessels during the development of injury (Fig. 1), seen in close relation to B cell-rich nodular infiltrates, which are likely to function as tertiary lymphoid organs.
Unilateral ureteric obstruction is a model of renal fibrosis, and we have adopted this model to undertake mechanistic studies into lymphangiogenesis. We have undertaken a series of macrophage depletion experiments using liposomal clodronate in order to determine whether macrophages contribute significantly to lymphangiogenesis. There was no significant difference in the number of lymphatic vessels with and without macrophage depletion.
In summary, we have developed an exciting model of CAI and have used this and other models to examine the process of lymphangiogenesis in the context of renal transplantation.
Figure 1. At 8 weeks there was a significant increase in lymphatic vessel number in allografts compared with isograft controls, and this was associated with increased fibrosis.
Publications
- Vass D, Hughes J, Marson L. Lymphangiogenesis in renal transplantation. Oral presentation, British Transplantation Society 2009; (Abstract).
- Vass D, Hughes J, Marson L. Renal lymphatics in health and disease. Oral presentation, European Society of Organ Transplantation 2009; (Abstract).
