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Three-dimensional imaging and single-cell transcriptomics of the human kidney implicate perturbation of lymphatics in alloimmunity [article]

Daniyal J Jafree, Benjamin Stewart, Maria Kolatsi-Joannou, Benjamin Davis, Hannah Mitchell, Lauren G Russell, Lucia Marinas del Rey, William J Mason, Byung Il Lee, Lauren Heptinstall, Gideon Pomeranz, Dale Moulding (+16 others)
2022 bioRxiv   pre-print

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https://web.archive.org/web/20221102111242/https://www.biorxiv.org/content/biorxiv/early/2022/10/28/2022.10.28.514222.full.pdf

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Studies of the structural and molecular features of the lymphatic vasculature, which clears fluid, macromolecules and leukocytes from the tissue microenvironment, have largely relied on animal models, with limited information in human organs beyond traditional immunohistochemical assessment. Here, we use three-dimensional imaging and single-cell RNA-sequencing to study lymphatics in the human kidney. We found a hierarchical arrangement of lymphatic vessels within human kidneys, initiating along
more » ... specialised nephron epithelium in the renal cortex and displaying a distinct, kidney-specific transcriptional profile. In chronic transplant rejection we found kidney allograft lymphatic expansion alongside a loss of structural hierarchy, with human leukocyte antigen-expressing lymphatic vessels infiltrating the medulla, presenting a putative target for alloreactive antibodies. This occurred concurrently with lymphatic vessels invading and interconnecting tertiary lymphoid structures at early stages of lymphocyte colonisation. Analysis of intercellular signalling revealed upregulation of co-inhibitory molecule-mediated CD4+ T cell-lymphatic crosstalk in rejecting kidneys, potentially acting to limit local alloimmune responses. Overall, we delineate novel structural and molecular features of human kidney lymphatics and reveal perturbations to their phenotype and transcriptome in the context of alloimmunity.
doi:10.1101/2022.10.28.514222 fatcat:5dzoxtlyxrb65ibplwbra7bvly
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Daniyal J Jafree, Benjamin Stewart, Maria Kolatsi-Joannou, Benjamin Davis, Hannah Mitchell, Lauren G Russell, Lucia Marinas del Rey, William J Mason, Byung Il Lee, Lauren Heptinstall, Gideon Pomeranz, Dale Moulding, Laura Wilson, Tahmina Wickenden, Saif Malik, Natalie Holroyd, Claire Walsh, Jennifer C Chandler, Kevin X Cao, Paul JD Winyard, Karen L Price, Adrian S Woolf, Marc Aurel Busche, Simon Walker-Samuel, Peter J Scambler, Reza Motallebzadeh, Menna R Clatworthy, David A Long. "Three-dimensional imaging and single-cell transcriptomics of the human kidney implicate perturbation of lymphatics in alloimmunity." bioRxiv (2022)