UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Interrogating the spatial and molecular profile of kidney lymphatic vessels in health and transplant rejection
  • Publication Type:
    Conference presentation
  • Authors:
    Jafree D, Kolatsi-Joannou M, Stewart B, Pomeranz G, Marinas Del Rey L, Mason W, WILSON L, Aktar T, Hepinstall H, Scambler P, Clatworthy M, Motallebzadeh R, Long D
  • Date:
    04/10/2021
  • Name of Conference:
    UK Kidney Week
  • Conference start date:
    04/10/2021
  • Conference finish date:
    07/10/2021
  • Conference URL:
Abstract
Introduction: Novel roles for lymphatic vessels, in addition to their established function of clearing excess tissue fluid, cells and small molecules from organs, are emerging in the modulation of diseases such as cancer and autoimmunity. In these contexts, it has been shown that lymphatic cells within lymph nodes possess immunoregulatory properties which promote immunological tolerance. An association between allograft function after kidney transplantation and the expansion of kidney lymphatics has been observed from histological sections of biopsies, however it is difficult to discern the spatial and molecular features of lymphatics in kidney health or transplant tolerance and rejection from histological features alone. not well known. Methods: We applied emerging technologies to interrogate lymphatic vessels in the human kidney. Wholemount immunolabelling and three-dimensional confocal microscopy were used to visualise lymphatic vessel architecture in non-transplanted donor kidneys and chronically rejecting renal allografts at cellular resolution. Further, computational analysis of a published single-cell transcriptome dataset was used to capture the gene expression of lymphatics and immune cell subsets from chronically rejecting and non-rejecting allograft biopsies. Results: In health, lymphatic vessels were found to run parallel to nephron segments in the cortex, but not the medulla, intermingling only with distal convoluted tubules but no other tubular segments. In chronic transplant rejection, these vessels expanded over seven-fold in density and infiltrated the renal medulla. By identifying a prototypic lymphatic gene expression pattern from single-cell transcriptome data, we found that lymphatics in rejecting allografts adopt an immunoregulatory signature akin to a tolerogenic region of the lymph node at steady-state. Specifically, lymphatics in rejecting allografts showed upregulation of key molecules implicated in antigen presentation such as HLA-DR. In line with these findings, lymphatics exhibited a lymph node sinus-like architecture surrounding lymphoid aggregates of T and B cells. Both three-dimensional imaging and single-cell transcriptome analysis implicated that lymphatics express immune checkpoints and chemokine sequestering receptors, each that may interact with distinct T cell subsets. Conclusion: We profile the three-dimensional architecture and spatial relationships of kidney lymphatic vessels in health and chronic allograft rejection. Both spatially and molecularly, we implicate that lymphatic vessels may act as a tolerogenic nidus in chronic renal transplant rejection. These results lay a foundation for functional studies to exploit kidney lymphatics and their immunoregulatory features as a therapeutic target in allograft longevity and to prevent transplant rejection.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers Show More
Author
Developmental Biology & Cancer Dept
Author
Div of Surgery & Interventional Sci
Author
Developmental Biology & Cancer Dept
Author
Department of Surgical Biotechnology
Author
UCL GOS Institute of Child Health
Author
Developmental Biology & Cancer Dept
Author
UCL GOS Institute of Child Health
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by