XXXX (+) monocytes with smooth muscle cell characteristics are reduced in @entity1 renal chronic transplant dysfunction.

@entity1 @entity5750 @entity1970 @entity740 @entity4071 @entity15008 @entity8233
In @entity740 ( @entity740 ), persistent (allo)immune-mediated inflammation eventually leads to tissue remodeling including @entity8233 formation in intragraft arteries. We previously showed that recipient-derived neointimal @entity1970 (+) smooth muscle-like cells are present in @entity1 renal allografts with @entity740 . @entity1 PBMC contain myeloid cells capable of differentiating into @entity1970 (+) cells in vitro; the phenotype of the ancestral subset is as yet unknown. This study aimed to investigate whether monocyte subsets contain cells with smooth muscle-like cell differentiation capacity and whether @entity740 in renal transplant recipients is associated with a shift in these monocyte subsets. To accomplish this goal, monocyte subsets from healthy controls were sorted based on @entity5750 and @entity4071 expression to investigate gene expression levels of mesenchymal markers @entity1970 and @entity15008 . @entity5750 (+)/ @entity4071 (++) monocytes displayed increased @entity1970 and @entity15008 mRNA expression compared with @entity5750 (++)/ @entity4071 (-) monocytes, suggesting increased differentiation potential toward smooth muscle-like cells. Flow cytometry revealed that in non- @entity740 transplant recipients the percentage of @entity5750 (+)/ @entity4071 (++) monocytes was reduced, with an even further reduction in @entity1 with @entity740 . To determine a potential correlation between @entity5750 (+)/ @entity4071 (++) monocytes and @entity1970 (+) cell outgrowth potential in vitro, PBMC of healthy controls and transplant recipients with and without @entity740 were cultured under fibrotic culture conditions, and indeed a significant correlation (p=0.0002, r=0.62) was observed. Finally, double staining for @entity1970 and @entity4071 revealed presence of @entity1970 (+) @entity4071 (+) cells in kidney explants from @entity740 @entity1 , albeit at very low numbers. Our data represent evidence that, compared to @entity5750 (++) @entity4071 (-) monocytes, @entity5750 (+) @entity4071 (++) monocytes have an increased expression of smooth muscle cell-associated genes. This monocyte subpopulation is reduced in renal transplant @entity1 with @entity740 , possibly due to selective migration into the allograft.
