Fibroblasts versus graft
The recipient's fibroblasts penetrate into the donor kidney with signs of rejection
Elena Kleshchenko, PCR.news
Currently, there is no effective therapy for rejection of a donor kidney. To better understand the processes of graft adaptation in the body, researchers from the USA and Qatar sequenced the RNA of single cells in tissue samples of a normal kidney and two transplanted kidneys — with signs of rejection and healthy. It turned out that more than half of the fibroblasts in the donor kidney with deteriorating function belong to the recipient.
Immune rejection of a donor kidney after transplantation remains a serious problem, despite the use of immunosuppressants. The use of anti-rejection therapy is hindered by an insufficiently complete understanding of the processes occurring in the transplanted organ. To find clues to immune disorders after transplantation, a team from Weill Cornell Medicine (Cornell University) and other research centers sequenced the RNA of single kidney cells and performed molecular phenotyping of infiltrating host cells and donor parenchymal cells
The authors of the article published in PLOS One (Suryawanshi et al. Detection of infiltrating fibroblasts by single-cell transcriptomics in human kidney allografts), conducted RNA sequencing of single cells using the Chromium platform from 10x Genomics. Three kidney biopsy samples were examined: normal kidney tissue from a living transplant donor, a kidney transplanted from a donor with deteriorating function and tubulointerstitial fibrosis, as well as a sample of a successfully transplanted kidney without signs of rejection. Biopsies were processed quickly, without cryopreservation. It was possible to obtain data on more than 7,200 individual cells.
12 large clusters of cell types were identified in the biopsies. To the surprise of the authors, 42 months after transplantation, one subtype of fibroblasts in the donor organ with a deterioration in function (and in quantitative terms more than half of fibroblasts) was received from the recipient, and not from the donor. Since the donor was male and the recipient was female, the identity of the cells could be determined by comparing the expression of genes located in the sex chromosomes.
In a donor kidney functioning normally, 84 months after transplantation, this was not observed: most of the fibroblasts belonged to the donor. (In this case, the donor was a woman and the recipient was a man.) In addition, the "dysfunctional" kidney was enriched with precursors of the cells of the proximal tubules of the nephron with increased expression of the gene contributing to fibrosis. The successfully transplanted kidney contained plasmoblasts with high expression of immunoglobulins, endothelial cells producing T-cell cytokines; cytotoxic T-cells were also present in it. Other unique cell types and conditions in donor kidneys have also been identified. Finally, transcriptomes of endothelial cell subtypes provided additional information about the allograft response.
According to the authors, transcriptomics of single cells has provided a new mechanistic understanding of the immune mechanisms of transplant rejection, which can pave the way for individualization of therapy for patients who received a donor kidney.
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