Sequencing of Physically Interacting Cells in Human Kidney Allograft Rejection Reveals Insights into Immune Cell Interactions
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE189536 | GEO | 2023/09/30
REPOSITORIES: GEO
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Project description:Crosstalk between neighboring cells underlines many biological processes, such as cell activation, differentiation and signaling. Current single-cell genomic technologies lack information of cell-cell interactions, as each cell is profiled separately following tissue dissociation. Here we present Physically Interacting Cells sequencing (PIC-seq), which combines fluorescently activated cell sorting of physically interacting cells along with massively parallel single-cell RNA-sequencing and computational modeling to systematically map in situ cellular interactions and characterize their molecular crosstalk. Focusing on interactions between T cells and dendritic cells (DC) in vitro and in vivo, we map T-DC interaction preferences, and discover regulatory T cells as the major T cell subtype interacting with DC. Analysis of T-DC pairs characterized interaction-specific transcription, including upregulation of a costimulatory program in rare interactions between pathogen-presenting DC and T cells. In summary, PIC-seq provides a new technology to profile cell-cell interactions and characterize interaction-specific pathways and target genes at high resolution.
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Project description:Remarkable advances have been made in the pathophysiology, diagnosis, and treatment of antibody-mediated rejection (ABMR) over the past decades, leading to improved graft outcomes. However, long-term failure is still high and effective treatment for chronic ABMR, an important cause of graft failure, has not yet been identified. Chronic ABMR has a relatively different phenotype from active ABMR and is a slowly progressive disease in which graft injury is mainly caused by de novo donor specific antibodies (DSA). Since most trials of current immunosuppressive therapies for rejection have focused on active ABMR, treatment strategies based on those data might be less effective in chronic ABMR. A better understanding of chronic ABMR may serve as a bridge in establishing treatment strategies to improve graft outcomes. In this in-depth review, we focus on the pathophysiology and characteristics of chronic ABMR along with the newly revised Banff criteria in 2017. In addition, in terms of chronic ABMR, we identify the reasons for the resistance of current immunosuppressive therapies and look at ongoing research that could play a role in setting better treatment strategies in the future. Finally, we review non-invasive biomarkers as tools to monitor for rejection.
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