The renal capsule: a vibrant and adaptive cell environment of the kidney in homeostasis, disease and aging

Korin, B.; Avraham, S.; Moncada, R.; Ho, T.; Tleugabulova, M. C.; Menon, H.; Darmanis, S.; Liang, Y.; Modrusan, Z.; Chalouni, C.; Victoria, C.; Rangell, L.; Havnar, C.; Ewart, W.; Jones, C.; Jiang, J.; Dunlap, D.; Dohse, M.; McKay, A.; Webster, J. D.; Durinck, S.; Shaw, A. S.

doi:10.1101/2023.05.11.540033

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bioRxiv · 10.1101/2023.05.11.540033

The renal capsule: a vibrant and adaptive cell environment of the kidney in homeostasis, disease and aging

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Abstract

The kidney is a complex organ that governs many physiological parameters. It is roughly divided into three parts, the renal pelvis, medulla, and cortex. Covering the cortex is the renal capsule, a serosal tissue that provides protection and forms a barrier for the kidney. Serosal tissues of many organs have been recently shown to play a vital role in homeostasis and disease. Analyses of the cells that reside in these tissues have identified distinct cell types with unique phenotypes. Here, we characterized this niche and found that it is mainly comprised of fibroblasts and macrophages, but also includes other diverse cell types. Characterizing renal capsule-associated macrophages, we found that they consist of a distinct subset (i.e., TLF+ macrophages) that is nearly absent in the kidney parenchyma. Injury, disease, and other changes that involve the kidney, affected the cell composition of the renal capsule, indicating its dynamic response to changes within the organ parenchyma. Lastly, we studied age-related changes in the renal capsule and found that aging affected the cell composition and inflammatory phenotype of macrophages, increased CD8 T cells and other lymphocyte counts, and promoted a senescence-associated phenotype in fibroblasts. Taken together, our data illustrate the complexity and heterogeneity of the renal capsule and its underlying changes during aging and disease, improving our understanding of the kidney serosa that may be valuable for novel renal therapies.

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Korin, B., Avraham, S., Moncada, R., Ho, T., Tleugabulova, M. C., Menon, H., Darmanis, S., Liang, Y., Modrusan, Z., Chalouni, C., Victoria, C., Rangell, L., Havnar, C., Ewart, W., Jones, C., Jiang, J., Dunlap, D., Dohse, M., McKay, A., Webster, J. D., Durinck, S., Shaw, A. S.. 2023-05-13. The renal capsule: a vibrant and adaptive cell environment of the kidney in homeostasis, disease and aging. https://doi.org/10.1101/2023.05.11.540033

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