Abstract
The lymphatics system has many diverse roles in the human body. These range from regulating fluid balance and fatty acid transport to serving as a conduit for leukocyte entry into lymphoid organs. While stromal cell populations are becoming increasingly recognised as important components of the immune response, the peripheral lymphatics are still commonly perceived as a passive conduit for immune cells. In contrast to this paradigm, the lymphatics are capable of responding to a wide range of pathogenic stimuli and secondary immune mediators, activating diverse, functional and stimulus dependant programs to these, with subsequent regulation of the effector function of multiple immune cell populations. In this review, we highlight papers that support the peripheral lymphatics as a crucial and active player in the immune response. We also interpret this evidence in the context of human disease pathogenesis and the potential for lymphatic-targeted therapeutic interventions.
Highlights
The lymphatics system runs parallel to the venous system [1]
The afferent lymphatic vessels primarily transport dendritic cells into the secondary lymph nodes, whilst efferent vessels facilitate the efflux of lymphocytes and antibodies from the lymph nodes [2,3]
While the lymphatics are often perceived as a passive conduit for fluid, fatty acids, and immune cells, evidence has emerged that suggests their role in orchestrating immune responses is active rather than passive
Summary
The lymphatics system runs parallel to the venous system [1]. Its primary immune-related functions are mediating the trafficking of immune cells between the periphery and secondary lymphoid tissues, and draining fluid and soluble immune mediators/antigens from affected sites. Lymphangiogenesis has a well-accepted role in mediating tumour metastases and the adverse outcomes associated with this [17] While these observations strongly support an active role of the peripheral lymphatics in the immune response, diseases and experimental models of 'primary' lymphatic dysfunction best highlight the role of the lymphatics in the immune response. Primary (and secondary) lymphoedema patients are characterised by global immune deficits including impaired wound healing, decreased immune defences and an increased susceptibility to infections [21] This same relationship between lymphatic and immune dysfunction is observed systemic sclerosis and lymphatic filariasis patients [22,23]. We highlight papers that demonstrate an active role for the peripheral lymphatics both in responding to, and regulating the immune response
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