Impact of Local Alloimmunity and Recipient Cells in Transplant Arteriosclerosis.

Circulation Research
Jingjing CaiQingbo Xu

Abstract

Transplant arteriosclerosis is the major limitation to long-term survival of solid organ transplantation. Although both immune and nonimmune cells have been suggested to contribute to this process, the complex cellular heterogeneity within the grafts, and the underlying mechanisms regulating the disease progression remain largely uncharacterized. We aimed to delineate the cellular heterogeneity within the allografts, and to explore possible mechanisms underlying this process. Here, we reported the transcriptional profiling of 11 868 cells in a mouse model of transplant arteriosclerosis by single-cell RNA sequencing. Unbiased clustering analyses identified 21 cell clusters at different stages of diseases, and focused analysis revealed several previously unknown subpopulations enriched in the allografts. Interestingly, we found evidence of the local formation of tertiary lymphoid tissues and suggested a possible local modulation of alloimmune responses within the grafts. Intercellular communication analyses uncovered a potential role of several ligands and receptors, including Ccl21a and Cxcr3, in regulating lymphatic endothelial cell-induced early chemotaxis and infiltration of immune cells. In vivo mouse experiments confirmed t...Continue Reading

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Citations

Sep 25, 2020·Circulation Research·Dawn M Fernandez, Chiara Giannarelli
May 14, 2021·Frontiers in Pharmacology·Mengqing JiangJingjing Cai
Jul 20, 2021·Frontiers in Immunology·Charlotte DomblidesMarie-Caroline Dieu-Nosjean
Sep 4, 2021·Circulation Research·Liujun JiangLi Zhang

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