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Objective: Mesenchymal stem cells (MSCs) show immunomodulatory functions. But the exact mechanism underlying these activities of MSCs is still not completely understood. There have been a few studies which have assessed the effects of these cells on dendritic cells (DCs) function. Given the importance of programmed cell death receptor-1 (PD-L1) and vitamin D receptor (VDR) expression in induction of tolerance in DCs, we were encouraged to investigate if one of the immunomodulatory functions of MSCs could be inducing upregulation of PD-L1 and VDR on DCs or not. Methods: DCs were co-cultured with MSCs or treated with them in transwell plates in the presence or absence of Lipopolysaccharide (LPS). Expression of PD-L1 and VDR mRNA and proteins in treated DCs were assessed by Real-time PCR and Western blot techniques. Furthermore, treated DCs were co-cultured with allogeneic T-cells, and T-cell proliferation and cytokine secretions in co-culture supernatants were assessed. Results: The results showed that PD-L1 but not VDR expression is significantly upregulated in the DCs co-cultured with MSCs. Furthermore, cell-to-cell contact and also presence of maturation inducers like LPS is necessary for this function. Moreover, our results indicated that MSCs could induce tolerogenic DCs (TolDCs) which could decrease the secretion of IL-2 by T-cells and inhibit T-cell proliferation as well as increase secretion of IL-10. Conclusions: Overall, our results show that MSCs may have several suppressive effects on immune responses by induction of TolDCs expressing more PD-L1 immunomodulatory molecule and change the cytokines profile of DCs and T-cells. [ABSTRACT FROM PUBLISHER]

Cytokines are important factors determining the outcome of transplantation. Since host ability in cytokine production may be affected by cytokine genes polymorphisms, the aim of the present study was to investigate the effect of IL-17, IL-23R and IL-21 gene polymorphisms in outcome of liver transplantation. A total of 200 liver transplant recipients were included in this study. IL-17 -197 A/G, IL-21 + 1472 G/T, IL-21 5250 C/T, and IL-23R C/A polymorphisms were evaluated by PCR-RFLP or ARMS-PCR methods. The serum levels of IL-17 and IL-21 in rejected and non-rejected groups were determined by ELISA method. The results showed that IL-23R AC carriers and C allele were significantly more frequent in patients with acute rejection than patients without rejection ( p = 0.01 and p = 0.0005, respectively). After gender classification, IL-23R AA and AC carriers were significantly more frequent in female patients ( p = 0.01, p = 0.01, respectively) and IL-23R AA and AC carriers and A allele were significantly more frequent in male patients ( p = 0.009, p = 0.02, p = 0.003, respectively). There is a significant association between CC genotype and C alleles of IL-23R and AR in the patients receiving allograft from living donor ( p = 0.0003 and p = 0.0008, respectively). Also, IL-23R AA and AC genotypes and C alleles showed a significant association with rejection in patients receiving allograft from cadaver donor ( p = 0.001, p = 0.002 and p = 0.02). The mentioned results indicate that IL-23R AC carriers and C allele have predictive values for acute rejection. AC genotype and C allele of IL-23R is a genetic risk factor for development of acute rejection. Also, AA and AC genotype of IL-23R is a sex dependent genetic risk factor for development of acute rejection. But this subject needs to be studied in different population. [ABSTRACT FROM AUTHOR]