Lymphatic Vessels in the Development of Tissue and Organ Rejection

Abstract

The lymphatic vascular system-amongst other tasks-is critically involved in the regulation of adaptive immune responses as it provides an important route for APC trafficking to secondary lymphatic organs. In this context, the cornea, which is the transparent and physiologically avascular "windscreen" of the eye, has served as an excellent in vivo model to study the role of the blood and lymphatic vasculature in mediating allogenic immune responses after transplantation. Especially the mouse model of high-risk corneal transplantation, where corneal avascularity is abolished by a severe inflammatory stimulus prior to keratoplasty, allows for comparison to other transplantations performed in primarily vascularized tissues and solid organs. Using this model, we recently demonstrated that especially lymphatic vessels, but not blood vessels, define the high-risk status of vascularized corneas and that anti(lymph)angiogenic treatment significantly promotes corneal allograft survival. Since evidence for lymphangiogenesis and its potential association with graft rejection is nowadays also present in solid organ transplantation, studies are currently addressing the potential benefits of anti(lymph)angiogenic treatment as a novel therapeutic concept also in solid organ grafting with promising initial results.

Lymphatic vessels regulate immune microenvironments in human and murine melanoma

“…However, the role of lymphangiogenesis in inflammation and immunity remains unclear. The abundant clinical and experimental evidence correlating lymphangiogenesis with tumor progression contrasts with reports that lymphangiogenesis in tissue transplantation can promote graft rejection (18), and further confounding the issue are reports suggesting that lymphangiogenesis promotes immune resolution in chronic inflammation (12,13). Therefore, it is likely that lymphatic vessels may serve multiple and complex roles in both the induction and resolution of local immune responses in acute versus chronic inflammation (19).…”

Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

“…The lymphatic network plays an important role in inflammatory and autoimmune diseases, cancer, lymphedema, graft rejection, and wound healing 17, 18, 19. The concept that lymphatic vessels could influence atherogenesis and lipoprotein transport has first been brought forward several decades ago 20, 21, 22.…”

Lymphangiogenesis in human corneal grafts that has evolved to re-transplantation

“…By observing table 2, however, we see that among these 7 patients, 5 presented lymphangiogenesis associated to hemangiogenesis, demonstrating that at this moment the role of the presence of lymphatic vessels associated to blood vessels is mainly suggested in the survival of corneal grafts. As previously mentioned, most studies on the importance of lymphangiogenesis in the rejection or survival of corneal grafts have been performed in murine models (8)(9)(10)(11)(12)(13)(14) . Some of these murine studies are according to our findings showing the role of hemangiogenesis and lymphangiogenesis in the rejection or survival of corneal grafts (10,11) .…”

“…However, it is known that any transplantation of solid or vascularized organ is accompanied by hemangiogenesis and lymphangiogenesis through the edges of the wound (8) . In this context, the cornea has worked as an excellent in vivo model to study the role of lymphatic and blood vasculature in the mediation of allogeneic immune responses after transplantation (9) . However, most studies on the importance of lymphangiogenesis in the rejection or survival of the corneal grafts have been held in murine models (8)(9)(10)(11)(12)(13)(14) .…”

“…In this context, the cornea has worked as an excellent in vivo model to study the role of lymphatic and blood vasculature in the mediation of allogeneic immune responses after transplantation (9) . However, most studies on the importance of lymphangiogenesis in the rejection or survival of the corneal grafts have been held in murine models (8)(9)(10)(11)(12)(13)(14) . Given the above, we aim at studying, through histopathological examination, the human corneal buttons that have lymphatic vessels along with the grafts from their previous and subsequent transplantations, assessing the time intervals required for successive surgeries.…”