Modulatory effect of rapamycin and tacrolimus ...
Document type :
Compte-rendu et recension critique d'ouvrage
Title :
Modulatory effect of rapamycin and tacrolimus on monocyte-derived dendritic cells phenotype and function
Author(s) :
Dahlqvist, Geraldine [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Cliniques Universitaires Saint-Luc [Bruxelles]
Renaud, Sarah [Auteur]
Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 [ONCO-THAI]
Institut de biologie de Lille - UMS 3702 [IBL]
Barjon, Clement [Auteur]
Université Catholique de Louvain = Catholic University of Louvain [UCL]
Lefebvre, Anthony [Auteur]
Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 [ONCO-THAI]
Aoudjehane, Lynda [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Horsmans, Yves [Auteur]
Cliniques Universitaires Saint-Luc [Bruxelles]
Delhem, Nadira [Auteur]
Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 [ONCO-THAI]
Institut de biologie de Lille - UMS 3702 [IBL]
Conti, Filomena [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
CHU Pitié-Salpêtrière [AP-HP]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Cliniques Universitaires Saint-Luc [Bruxelles]
Renaud, Sarah [Auteur]
Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 [ONCO-THAI]
Institut de biologie de Lille - UMS 3702 [IBL]
Barjon, Clement [Auteur]
Université Catholique de Louvain = Catholic University of Louvain [UCL]
Lefebvre, Anthony [Auteur]
Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 [ONCO-THAI]
Aoudjehane, Lynda [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
Horsmans, Yves [Auteur]
Cliniques Universitaires Saint-Luc [Bruxelles]
Delhem, Nadira [Auteur]
Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 [ONCO-THAI]
Institut de biologie de Lille - UMS 3702 [IBL]
Conti, Filomena [Auteur]
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [ICAN]
CHU Pitié-Salpêtrière [AP-HP]
Journal title :
Immunobiology
Pages :
152031
Publisher :
Elsevier
Publication date :
2021
ISSN :
0171-2985
English keyword(s) :
Tolerance
IDO
Immunosuppressive drugs
IDO
Immunosuppressive drugs
HAL domain(s) :
Sciences du Vivant [q-bio]/Immunologie/Immunothérapie
English abstract : [en]
Background: Immunosuppressive-drugs are needed after solid organ transplantation to prevent allograft rejection but induce severe side effects. Understanding the alloimmune response is critical to modulate it and to achieve ...
Show more >Background: Immunosuppressive-drugs are needed after solid organ transplantation to prevent allograft rejection but induce severe side effects. Understanding the alloimmune response is critical to modulate it and to achieve graft operational tolerance. The role of regulatory T cells and tolerogenic dendritic cells (Tol-DCs) is undoubtedly essential in tolerance induction. Tacrolimus is considered as the cornerstone of immunosuppression in solid organ transplantation. mTOR inhibitor such as rapamycin are thought to induce tolerance and are used as anticancer drugs in several cancers. The aim of this study was to better understand the effect of these immunosuppressive drugs on the differentiation, maturation and function of human monocyte derived dendritic cells (DCs).Material and methods: DCs were differentiated from monocytes of healthy donors with either rapamycin (Rapa-DCs) or tacrolimus (Tac-DCs). The phenotype was evaluated by flow cytometry analysis. The production of pro- and anti-inflammatory cytokines was assessed by ELISA. The mRNA expression level of IDO and PD-L1 was assessed by RTqPCR. Mixed leukocytes reactions were performed to analyse suppressive activity of DCs.Results: Rapa-DC were characterised by a lower expression of the co-stimulatory molecules and CD83 than control-DCs (CTR-DC) (p < 0.05). In contrast, tacrolimus had no effect on the expression of surface markers compared to CTR-DCs. Rapamycin reduced both IL-12 and IL-10 secretions (p < 0.05). Rapa-DCs had a suppressive effect on CD4+ allogenic T cells compared to CTR-DCs (p < 0.05). However, neither Rapa-DCs nor Tac-DCs favoured the emergence of a CD4+CD25highFoxp3+ population compared to CTR-DCs. Surprisingly, Rapa-DCs had a reduced expression of IDO and PD-L1 compared to Tac-DCs and CTR-DCs.Conclusion: Rapa-DCs exhibit an incomplete phenotypic tolerogenic profile. To our knowledge this is the first paper showing a reduction of expression of pro-tolerogenic enzyme IDO in DCs. Tacrolimus does not change the phenotypical or functional characteristics of moDCs.Show less >
Show more >Background: Immunosuppressive-drugs are needed after solid organ transplantation to prevent allograft rejection but induce severe side effects. Understanding the alloimmune response is critical to modulate it and to achieve graft operational tolerance. The role of regulatory T cells and tolerogenic dendritic cells (Tol-DCs) is undoubtedly essential in tolerance induction. Tacrolimus is considered as the cornerstone of immunosuppression in solid organ transplantation. mTOR inhibitor such as rapamycin are thought to induce tolerance and are used as anticancer drugs in several cancers. The aim of this study was to better understand the effect of these immunosuppressive drugs on the differentiation, maturation and function of human monocyte derived dendritic cells (DCs).Material and methods: DCs were differentiated from monocytes of healthy donors with either rapamycin (Rapa-DCs) or tacrolimus (Tac-DCs). The phenotype was evaluated by flow cytometry analysis. The production of pro- and anti-inflammatory cytokines was assessed by ELISA. The mRNA expression level of IDO and PD-L1 was assessed by RTqPCR. Mixed leukocytes reactions were performed to analyse suppressive activity of DCs.Results: Rapa-DC were characterised by a lower expression of the co-stimulatory molecules and CD83 than control-DCs (CTR-DC) (p < 0.05). In contrast, tacrolimus had no effect on the expression of surface markers compared to CTR-DCs. Rapamycin reduced both IL-12 and IL-10 secretions (p < 0.05). Rapa-DCs had a suppressive effect on CD4+ allogenic T cells compared to CTR-DCs (p < 0.05). However, neither Rapa-DCs nor Tac-DCs favoured the emergence of a CD4+CD25highFoxp3+ population compared to CTR-DCs. Surprisingly, Rapa-DCs had a reduced expression of IDO and PD-L1 compared to Tac-DCs and CTR-DCs.Conclusion: Rapa-DCs exhibit an incomplete phenotypic tolerogenic profile. To our knowledge this is the first paper showing a reduction of expression of pro-tolerogenic enzyme IDO in DCs. Tacrolimus does not change the phenotypical or functional characteristics of moDCs.Show less >
Language :
Anglais
Popular science :
Non
Source :
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