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      Immune cell composition in normal human kidneys

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          Abstract

          An understanding of immunological mechanisms in kidney diseases has advanced using mouse kidneys. However, the profiling of immune cell subsets in human kidneys remains undetermined, particularly compared with mouse kidneys. Normal human kidneys were obtained from radically nephrectomised patients with urogenital malignancy (n = 15). Subsequently, human kidney immune cell subsets were analysed using multicolor flow cytometry and compared with subsets from C57BL/6 or BALB/c mice under specific pathogen-free conditions. Twenty kidney sections from healthy kidney donors or subjects without specific renal lesions were additionally analysed by immunohistochemistry. In human kidneys, 47% ± 12% (maximum 63%) of immune cells were CD3 + T cells. Kidney CD4 + and CD8 + T cells comprised 44% and 56% of total T cells. Of these, 47% ± 15% of T cells displayed an effector memory phenotype (CCR7 CD45RA CD69 ), and 48% ± 19% were kidney-resident cells (CCR7 CD45RA CD69 +). However, the proportions of human CD14 + and CD16 + myeloid cells were approximately 10% of total immune cells. A predominance of CD3 + T cells and a low proportion of CD14 + or CD68 + myeloid cells were also identified in healthy human kidney sections. In mouse kidneys, kidney-resident macrophages (CD11b low F4/80 high) were the most predominant subset (up to 50%) but the proportion of CD3 + T cells was less than 20%. These results will be of use in studies in which mouse results are translated into human cases under homeostatic conditions or with disease.

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          The immune system and kidney disease: basic concepts and clinical implications.

          The kidneys are frequently targeted by pathogenic immune responses against renal autoantigens or by local manifestations of systemic autoimmunity. Recent studies in rodent models and humans have uncovered several underlying mechanisms that can be used to explain the previously enigmatic immunopathology of many kidney diseases. These mechanisms include kidney-specific damage-associated molecular patterns that cause sterile inflammation, the crosstalk between renal dendritic cells and T cells, the development of kidney-targeting autoantibodies and molecular mimicry with microbial pathogens. Conversely, kidney failure affects general immunity, causing intestinal barrier dysfunction, systemic inflammation and immunodeficiency that contribute to the morbidity and mortality of patients with kidney disease. In this Review, we summarize the recent findings regarding the interactions between the kidneys and the immune system.
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            Location, location, location: Tissue resident memory T cells in mice and humans

            The discovery of T cells resident in diverse tissues has altered our understanding of adaptive immunity to encompass site-specific responses mediated by tissue-adapted memory T cells throughout the body. Here, we discuss the key phenotypic, transcriptional, and functional features of these tissue-resident memory T cells (TRM) as established in mouse models of infection and translated to humans by novel tissue sampling approaches. Integration of findings from mouse and human studies may hold the key to unlocking the potential of TRM for promoting tissue immunity and preventing infection.
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              Spatiotemporal immune zonation of the human kidney

              Tissue-resident immune cells are important for organ homeostasis and defense. The epithelium may contribute to these functions directly or by cross-talk with immune cells. We used single-cell RNA sequencing to resolve the spatiotemporal immune topology of the human kidney. We reveal anatomically defined expression patterns of immune genes within the epithelial compartment, with antimicrobial peptide transcripts evident in pelvic epithelium in the mature, but not fetal, kidney. A network of tissue-resident myeloid and lymphoid immune cells was evident in both fetal and mature kidney, with postnatal acquisition of transcriptional programs that promote infection-defense capabilities. Epithelial-immune cross-talk orchestrated localization of antibacterial macrophages and neutrophils to the regions of the kidney most susceptible to infection. Overall, our study provides a global overview of how the immune landscape of the human kidney is zonated to counter the dominant immunological challenge.
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                Author and article information

                Contributors
                dlee5522@snu.ac.kr
                hansway80@gmail.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                24 September 2020
                24 September 2020
                2020
                : 10
                : 15678
                Affiliations
                [1 ]GRID grid.31501.36, ISNI 0000 0004 0470 5905, Department of Biomedical Sciences, , Seoul National University College of Medicine, ; 103 Daehakro, Jongno-gu, Seoul, 03080 South Korea
                [2 ]GRID grid.31501.36, ISNI 0000 0004 0470 5905, Department of Internal Medicine, , Seoul National University College of Medicine, ; 103 Daehakro, Jongno-gu, Seoul, 03080 South Korea
                [3 ]GRID grid.31501.36, ISNI 0000 0004 0470 5905, Department of Urology, , Seoul National University College of Medicine, ; 103 Daehakro, Jongno-gu, Seoul, 03080 South Korea
                [4 ]GRID grid.31501.36, ISNI 0000 0004 0470 5905, Department of Pathology, , Seoul National University College of Medicine, ; 103 Daehakro, Jongno-gu, Seoul, 03080 South Korea
                Article
                72821
                10.1038/s41598-020-72821-x
                7515917
                32973321
                0bae87ec-7e7e-4951-b4af-51f68dd50f9a
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 24 February 2020
                : 31 August 2020
                Funding
                Funded by: BK21-plus education program
                Funded by: FundRef http://dx.doi.org/10.13039/501100004332, Seoul National University Hospital;
                Award ID: 0420180700
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100003725, National Research Foundation of Korea;
                Award ID: 2020R1F1A1049632
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                translational immunology,nephrology
                Uncategorized
                translational immunology, nephrology

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