Lymph Node Transfer Decreases Swelling And Restores Immune Function In A Transgenic Model Of Lymphedema
Jung-Ju Huang, MD, Jason C. Gardenier, MD, Geoffrey E. Hespe, BS, Gabriela D. García Nores, MD, Raghu P. Kataru, PhD, Jessie Z. Yu, MD, Babak J. Mehrara, MD FACS.
Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Lymphedema is a morbid disease and lymph node transfer (LNT) is considered the most promising treatment. The mechanism of LNT remains unclear and its effectiveness in restoring immune function is not well explored. The purpose of this study was therefore to analyze lymphatic and immune function after LNT.
Hindlimb lymphedema was induced in a transgenic mouse model by ablating the lymphatic system using diphtheria toxin. Two weeks later, experimental animals underwent popliteal LNT while controls were treated with popliteal incision alone. Limb swelling, immune cell trafficking, and immune responses were then analyzed 8 weeks later.
LNT animals had a marked (85%) reduction in foot swelling from baseline (i.e. 2 weeks after lymphatic ablation); in contrast, control animals had no improvement in swelling over this period of time. These measurements were confirmed with histological studies demonstrating a more than 90% increase in adipose deposition in the control animals as compared with LNT. In addition, animals treated with LNT had decreased infiltration of T cells and marked increase in lymphangiogenesis and lymphatic regeneration. Moreover, animals treated with LNT were able to traffic dendritic cells to their lymph nodes (426% increase) and had significant increases in antibody responses as compared with controls. In response to DNFB, systemic immune responses were restored in LNT group.
LNT markedly induces lymphangiogenesis and improves lymphatic function in a mouse model of lymphedema. Transplanted lymph nodes maintain immunologic function and can support migration of antigen presenting cells.
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