Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Abstract

Background: Lymphatic vessels transport lymph away from microvascular beds into the cardiovascular system. The basic function of the lymphatic system include absorption of wa ter and macromolecules in the interstitial fluid, which plays an important role in maintaining osmotic balance of the body. Recent studies have shown that lymphangiogenesis is associated with tumor metabolism, injury repair, and chron ic inflammation, and deteriorates disease progression via immune cell trafficking. Summary: Renal interstitial lymph angiogenesis is found in patients with chronic kidney dis ease and a series of animal models of renal fibrosis. Lymphat ic vessels transfer antigen and antigenpresenting cells from peripheral tissues to lymph nodes, which initiates adaptive immunity and in turn deteriorates renal inflammation and renal fibrosis, even in nonautoimmune renal diseases. Key Messages: This review summarizes the latest findings on how lymphatics participate in the progression of chronic kid ney disease. This discussion will serve to highlight the role of adaptive immunity in noninfectious and nonautoimmune nephropathy, in order to provide new ideas and methods for prevention and treatment of kidney diseases.

Eplerenone reduces lymphangiogenesis in the contralateral kidneys of UUO rats

“…However, this study revealed that lymphangiogenesis exacerbated UUO-induced contralateral intrarenal inflammation and subsequent fibrosis, and eplerenone inhibited lymphangiogenesis and alleviated renal injury. These findings are consistent with those studies of lymphangiogenesis in other CKDs, such as lupus nephritis, antineutrophil cytoplasmic antibody-associated nephritis, tubulointerstitial nephritis, focal segmental glomerulosclerosis, crescentic nephritis, type II diabetic nephropathy, and IgA nephropathy, which exhibit significantly increased lymphangiogenesis compared with controls 4 , 19 , 20 . During chronic inflammation, lymphangiogenesis is a kind of disorderly expansion that can hinder the clearance of immune cells, leading to the accumulation of macrophages, dendritic cells, T and B lymphocytes, and fibroblasts, thereby exacerbating the chronic inflammatory response and ultimately leading to fibrosis 21 .…”

Evaluation Effects of Cefepime and Ceftriaxone on Renal Function Tests in Albino Male Rats

“…This initial phase of antigen presentation T cell activation is followed by a period of immune response integration [22], The effector phase that follows is Humoral factors released by infiltrating and residual renal cells act as mediators. Bidirectional communication between enlisted invading inflammatory cells and renal parenchyma, either via direct contact or via local soluble cytokines, eventually regulates The progression and severity of renal contribution [23].…”

Angiogenesis—An Emerging Role in Organ Fibrosis

“…Organ lymphatic vessels can reabsorb tissue fluid back to the circulatory system to maintain tissue environmental homeostasis. In addition to tumors [ 1 , 2 , 3 ], organ transplantation [ 4 ], inflammation [ 5 , 6 ], and wound healing [ 7 ], the role of lymphangiogenesis in organ fibrosis has gradually attracted attention in recent years, such as in renal fibrosis [ 6 , 8 , 9 , 10 , 11 ], liver fibrosis [ 12 , 13 ], cardiac fibrosis [ 14 , 15 , 16 , 17 ], pulmonary fibrosis [ 18 , 19 , 20 , 21 ], tumor fibrosis [ 22 ] and peritoneal fibrosis [ 23 , 24 ]. Increasing evidence suggests that lymphangiogenesis is related to the onset and progression of fibrotic disease, and VEGFC/VEGFR3 is central in lymphangiogenesis.…”