Session Name: Tolerance / Immune Deviation
Session Date & Time: None. Available on demand.
*Purpose: Tissue-resident immune cells reside within distinct niches across organs, where they sustain tissue homeostasis and rapidly respond to perturbations in the local microenvironment. Across these niches, immune cells adopt tissue-specific fates differing from circulating immune populations, and play important roles in directing immune responses. In the context of transplantation, understanding the contributions of resident immune cells to tissue homeostasis is key for defining aberrant immune responses following transplantation and developing new tolerance-promoting strategies to prevent allograft disease.
*Methods: To delineate the role of tissue-resident immune cells in kidney homeostasis and define their interactions with parenchymal cells and other immune cells, we performed single-cell RNA sequencing of 19 healthy kidney samples from living kidney donors.
*Results: Parenchymal populations from glomerular (podocytes, endothelial cells) and tubulointerstitial compartments (Loop of Henle, distal convoluted tubule, principal cells and intercalated cells) are featured in our map. Immune cells comprise <1% of healthy human kidney, differing from prior studies of deceased donor or rejected kidneys. To enrich for the capture of immune cells and their signatures, CD45-enrichment was performed on 10 of the samples. Immune infiltrates include distinct populations of T cells, monocytes, macrophages, B cells, and innate lymphoid cells. Using computational approaches, we are able to predict cellular interactions between immune and parenchymal cells at homeostasis, as well as define key factors that differentiate kidney-resident immune populations. Ongoing studies are functionally characterizing kidney-resident immune cells and validating predicted interactions with parenchymal populations.
*Conclusions: This comprehensive map of healthy human kidney at the single-cell level provides important insights into the functions of kidney-resident immune cells at homeostasis, and is an important reference to compare immunologic changes that occur with various kidney pathologies and in transplantation.
To cite this abstract in AMA style:Crome SQ, Szusz JM, McEvoy C, An J, Clotet-Freixas S, MacParland SA, Bader GD, Konvalinka A. Tissue-Specific Features of Immunity Revealed by Single-cell RNA Sequencing of Healthy Human Kidney [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/tissue-specific-features-of-immunity-revealed-by-single-cell-rna-sequencing-of-healthy-human-kidney/. Accessed June 11, 2021.
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