Mathews, J. A. | Search bioRxiv

bioRxiv2023

Cell therapy with IL-10-producing group 2 innate lymphoid cells suppresses Graft-versus-Host disease

IL-10 producing group 2 innate lymphoid cells (ILC210) have immunoregulatory functions, and limit harmful immune responses across various tissues. Despite their crucial roles in maintaining immune homeostasis, the cell therapy potential of human ILC210 has not been demonstrated, due to both limited numbers in human peripheral blood and lack of definitive markers for identification. Here, we isolate and expand circulating human ILC210, and assess their cell therapy potential in a humanized model of Graft-versus-Host Disease (GVHD). Cell therapy with human ILC210 decreased GVHD severity and prolonged survival of NOD-scid IL2R{gamma}null (NSG) mice. Adoptive transfer of ILC210 inhibited pathogenic T cell proliferation and intestinal infiltration, and suppressed CD4+ Th1 and CD8+ Tc1 cells in an IL-4 and IL-10 dependent manner. Critically, increased proportions of ILC2s did not correlate with higher rates of cancer relapse in HSCT recipients, and adoptive transfer of ILC210 did not compromise graft-versus-leukemic (GVL) effects in a humanized model. Finally, we identify CD49d and CD86 as novel markers that discriminate ILC210 from conventional ILC2s. Collectively, these findings demonstrate the potential of harnessing ILC210 in cell therapies for GVHD and other immune-driven pathologies.

immunology↗

bioRxiv2021

Single-cell profiling of healthy human kidney reveals features of sex-based transcriptional programs and tissue-specific immunity

Maintaining organ homeostasis requires complex functional synergy between distinct cell types, a snapshot of which is glimpsed through the simultaneously broad and granular analysis provided by single-cell atlases. Knowledge of the transcriptional programs underpinning the complex and specialized functions of human kidney cell populations at homeostasis is limited by difficulty accessing healthy, fresh tissue. Here, we present a single-cell perspective of healthy human kidney from 19 living donors, with equal contribution from males and females, profiling the transcriptome of 27677 high-quality cells to map healthy kidney at high resolution. Our sex-balanced dataset revealed sex-based differences in gene expression within proximal tubular cells, specifically, increased anti-oxidant metallothionein genes in females and the predominance of aerobic metabolism-related genes in males. Functional differences in metabolism were confirmed between male and female proximal tubular cells, with male cells exhibiting higher oxidative phosphorylation and higher levels of energy precursor metabolites. Within the immune niche, we identified kidney-specific lymphocyte populations with unique transcriptional profiles indicative of kidney-adapted functions and validated findings by flow cytometry. We observed significant heterogeneity in resident myeloid populations and identified an MRC1+ LYVE1+ FOLR2+ C1QC+ population as the predominant myeloid population in healthy kidney. This study provides a detailed cellular map of healthy human kidney, revealing novel insights into the complexity of renal parenchymal cells and kidney-resident immune populations.

immunology↗