The Role of Lymphatic Vessels in Renal Injury

Abstract

Progressive kidney diseases are characterized by the recruitment of inflammatory cells to the tubulointerstitium, tubular atrophy and fibrosis. The number of lymphatic vessels increases in the interstitium during this process (i.e. neolymphangiogenesis). Here we will describe the current evidence for neolymphangiogenesis during renal injury, summarize the major factors involved and discuss the functional consequences. Data are emerging that central profibrotic players like TGF-β also mediate the release of lymphangiogenic factors such as VEGF-C and VEGF-D in the kidney. Furthermore, in other organs activation of TGF-β by VEGF-C has been described. The complex interactions of profibrotic and lymphangiogenic factors might explain why lymphangiogenesis was found to be associated with fibrosis in some models, but a reduction in fibrosis in others. It is likely that the functional consequences of lymphangiogenesis depend on the stage of the disease course and the microenvironment where it takes place. Studies are needed where lymphangiogenesis is switched on or off at defined time points. However such data are not yet available in models of renal diseases.

Role of Lymphatics in Immunity - Introduction

“…This collection of review articles addresses the critical immune roles of the lymphatics system and highlights the importance of these immune mechanisms in specific organs and diseases [1][2][3][4][5][6][7][8][9][10].…”

“…A number of articles in this special issue also review the role of the lymphatics in mediating local innate and adaptive immune responses in peripheral sites [1,3,5,[7][8][9]. One lymphatic-dependent mechanism for maintaining local immune homeostasis is the removal of interstitial fluid and cytokines/chemokines from local sites, to allow for the resolution of inflammation and effective wound healing [1,5,[7][8][9].…”

“…One lymphatic-dependent mechanism for maintaining local immune homeostasis is the removal of interstitial fluid and cytokines/chemokines from local sites, to allow for the resolution of inflammation and effective wound healing [1,5,[7][8][9]. Interestingly, lymphatic contractility and dilation are central to lymphatic drainage function and can be induced by local immune molecules such as histamine and TNFα, which implies a reciprocal relationship between lymphatic drainage and immunity [5,9].…”

“…Three articles highlight the importance of the immune roles of the lymphatics from the context of different organ systems [1,5,7]. Chauhan et al [1] review the role of the lymphatics in corneal inflammation and transplantation.…”

“…Mathias et al [5] review the critical role of the lymphatics in gastrointestinal immune homeostasis and in the pathophysiology of inflammatory bowel disease and food allergy. Finally, Seeger et al [7] review the importance of lymphangiogenesis in the pathophysiology of renal injury and disease. One recurrent trend from these articles is the apparent ability of the lymphatics to mediate both positive and negative immune-outcomes [1,5,7].…”