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- Ingelsten, Madeleine, et al.
(författare)
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Rapid Increase of Interleukin-10 Plasma Levels After Combined Auxiliary Liver-Kidney Transplantation in Presensitized Patients
- 2014
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 98:2, s. 208-215
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Tidskriftsartikel (refereegranskat)abstract
- Background. After transplantation, donor dendritic cells (DCs) in the grafted organ are activated by an ischemia/reperfusion-induced inflammatory process that induces their migration to the recipient's secondary lymphoid tissues. The subsequent interaction between migrated and mature donor DCs, recipient T cells, and natural killer (NK) cells is proposed to be crucial in directing host immune reactions toward allograft rejection. A liver transplant is less prone to induce rejection compared with most other solid organ transplants, and simultaneous transplantation of liver and kidney is known to improve the clinical outcome of kidney transplantation. Methods and Results. Here we show that liver as well as combined auxiliary liver-kidney transplantation in patients induces a rapid increase in plasma interleukin-10 (IL-10) to levels that are significantly higher than those seen after standard kidney transplantation. Addition of IL-10 during in vitro maturation of human monocyte-derived DCs with ischemia/reperfusion-associated factors was found to affect phenotypic DC maturation significantly. Addition of IL-10 inhibited DC production of the NK cell- and T cell-recruiting chemokines CXCL9, CXCL10 and CXCL11. Conclusion. Our findings indicate that liver transplantation induces a substantial systemic release of IL-10, which may inhibit T cell- and NK cell- mediated rejection processes toward the transplanted liver and concurrently transplanted kidney.
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| 2. |
- Liu, Peidi, et al.
(författare)
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Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy
- 2017
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Ingår i: Journal of the American Society of Nephrology. - : AMER SOC NEPHROLOGY. - 1046-6673 .- 1533-3450. ; 28:10, s. 2961-2972
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Tidskriftsartikel (refereegranskat)abstract
- IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22). Using curated glomerular cell type specific genes from the published literature, we found differential expression of a much higher percentage of mesangial cell positive standard genes than podocyte-positive standard genes in IgAN. Principal coordinate analysis of expression data revealed clear separation of patient and control samples on the basis of mesangial but not podocyte cell positive standard genes. Additionally, patient clinical parameters (serum creatinine values and eGFRs) significantly correlated with Z scores derived from the expression profile of mesangial cell positive standard genes. Among patients grouped according to Oxford MEST score, patients with segmental glomerulosclerosis had a significantly higher mesangial cell positive standard gene Z score than patients without segmental glomerulosclerosis. By investigating mesangial cell proteomics and glomerular transcriptomics, we identified 22 common pathways induced in mesangial cells by gd-IgA, most of which mediate inflammation. The genes, proteins, and corresponding pathways identified provide novel insights into the pathophysiologic mechanisms leading to IgAN.
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