Chronic Rejection of Cardiac Allografts Is Associated With Increased Lymphatic Flow and Cellular Trafficking

Edwards, Lindsey; Nowocin, Anna; Jafari, Nazila; Meader, Lucy; Brown, Kathryn; Sarde, Aurélien; Lam, Carolyn S.P.; Murray, Alex; Wong, Wilson

doi:10.1161/circulationaha.117.028533

Cited by 34 publications

(36 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This led to LV activation, increasing inflammation within cardiac allografts, whereas pharmacological inhibition of VEGF‐C/VEGFR3 reduced both acute and chronic cardiac allograft rejection (Figure A). In line with the immunomodulatory role of LVs and lymphangiogenesis in heart transplantation, a recent report demonstrated that lymphatic flow is significantly increased in murine heart allografts . Of note, this increased lymphatic flow was correlated with an increase in the number of donor‐derived cells in the mediastinal draining LNs and an increase in cardiac allograft vasculopathy (CAV), with increased graft infiltration by CD4 + T cells, CD8 + T cells, and CD68 + macrophages .…”

Section: Role Of Lymphangiogenesis In Solid Organ Transplantationmentioning

confidence: 74%

“…11 Of note, this increased lymphatic flow was correlated with an increase in the number of donor-derived cells in the mediastinal draining LNs and an increase in cardiac allograft vasculopathy (CAV), with increased graft infiltration by CD4 + T cells, CD8 + T cells, and CD68 + macrophages. 11 Along these lines, targeted delivery of immunotherapeutics to the LNs prolonged cardiac allograft survival in a mouse model, suggesting the transport of immune cells (and antigens) via the lymphatics to the draining LNs exacerbates cardiac allograft rejection. 12 Together, cardiac lymphatics remain an untapped avenue for therapeutic intervention in cardiovascular health and disease.…”

Section: Heart Transplantationmentioning

confidence: 99%

See 1 more Smart Citation

Lymphatic vessels in solid organ transplantation and immunobiology

Wong

2020

American Journal of Transplantation

View full text Add to dashboard Cite

endothelial hyaluronan receptor 1; MALT, mucosa-associated lymphoid tissue; mTOR, mechanistic target of rapamycin (also known as mammalian target of rapamycin); mTORC1, mechanistic target of rapamycin complex 1; NFAT, nuclear factor of activated T cells; NFκB, nuclear factor kappa B; NRP2, neuropilin 2; PDPN, podoplanin; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PROX1, prospero homeobox transcription factor 1; SLO, secondary lymphoid organ; TGFβ1, transforming growth factor beta 1; TLO, tertiary lymphoid organ; TNFα, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor; VEGF-A, vascular endothelial growth factor A; VEGF-C, vascular endothelial growth factor C; VEGF-D, vascular endothelial growth factor D; VEGFR3, vascular endothelial growth factor receptor 3 (known as Flt4 in the mouse).

show abstract

Section: Role Of Lymphangiogenesis In Solid Organ Transplantationmentioning

confidence: 74%

Section: Heart Transplantationmentioning

confidence: 99%

Lymphatic vessels in solid organ transplantation and immunobiology

Wong

2020

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…LVs have been found to play a pivotal role in immune-related diseases in the recent two decades. A large amount of literature reports that lymphangiogenesis is often associated with pathological conditions, such as tumor metastasis [42], injury repair [43], and chronic inflammation [44]. Renal lymphangiogenesis is associated with renal fibrosis, inflammation, and transplant rejection.…”

Section: Lymphangiogenesis and Kidney Diseasementioning

confidence: 99%

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Pei

Zeng

et al. 2020

Kidney Dis

View full text Add to dashboard Cite

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.

show abstract

“…Significant correlation was observed between heightened and sustained lymphatic flow in allogeneic hearts versus syngeneic controls. Interestingly, early measurements of LFI (after 1 week) were significantly greater in syngeneic hearts [112]. Such observations suggest a temporal regulation of lymphangiogensis that is defective with allograft vasculopathy and may be targeted for therapy.…”

Section: Direct Mechanisms Of Cav By Phagocytesmentioning

confidence: 99%

Acute and chronic phagocyte determinants of cardiac allograft vasculopathy

Glinton

DeBerge

Yeap³

et al. 2018

Semin Immunopathol

View full text Add to dashboard Cite

Post-transplant immunosuppression has reduced the incidence of T cell-mediated acute rejection, yet long-term cardiac graft survival rates remain a challenge. An important determinant of chronic solid organ allograft complication is accelerated vascular disease of the transplanted graft. In the case of cardiac allograft vasculopathy (CAV), the precise cellular etiology remains inadequately understood; however, histologic evidence hints at the accumulation and activation of innate phagocytes as a causal contributing factor. This includes monocytes, macrophages, and immature dendritic cell subsets. In addition to crosstalk with adaptive T and B immune cells, myeloid phagocytes secrete paracrine signals that directly activate fibroblasts and vascular smooth muscle cells, both of which contribute to fibrous intimal thickening. Though maladaptive phagocyte functions may promote CAV, directed modulation of myeloid cell function, at the molecular level, holds promise for tolerance and prolonged cardiac graft function.

show abstract

Chronic Rejection of Cardiac Allografts Is Associated With Increased Lymphatic Flow and Cellular Trafficking

Abstract: Chronic rejection results in increased lymphatic flow from the donor graft to draining lymph nodes, which may be a factor in promoting cellular trafficking, alloimmunity, and cardiac allograft vasculopathy.

Cited by 34 publications

References 42 publications

Lymphatic vessels in solid organ transplantation and immunobiology

Lymphatic vessels in solid organ transplantation and immunobiology

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Acute and chronic phagocyte determinants of cardiac allograft vasculopathy

Contact Info

Product

Resources

About