Pairing of single-cell RNA analysis and T cell antigen receptor profiling indicates breakdown of T cell tolerance checkpoints in atherosclerosis
نویسندگان
چکیده
Abstract Atherosclerotic plaques form in the inner layer of arteries triggering heart attacks and strokes. Although T cells have been detected atherosclerosis, tolerance dysfunction as a disease driver remains unexplored. Here we examine checkpoints atherosclerotic plaques, artery tertiary lymphoid organs lymph nodes mice burdened by advanced via single-cell RNA sequencing paired with cell antigen receptor sequencing. Complex patterns deteriorating peripheral were observed being most pronounced followed organs, blood. Affected included clonal expansion CD4 + , CD8 regulatory cells; aberrant tolerance-regulating transcripts clonally expanded exhaustion; reg –TH 17 conversion; dysfunctional presentation. Moreover, RNA-sequencing profiles human revealed that mouse was shared coronary carotid plaques. Thus, our data support concept atherosclerosis bona fide autoimmune targeting arterial wall.
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ژورنال
عنوان ژورنال: Nature Cardiovascular Research
سال: 2023
ISSN: ['2731-0590']
DOI: https://doi.org/10.1038/s44161-023-00218-w