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Modulating dendritic cells (DC) from immunogenic to tolerogenic responses: A novel mechanism of AZA/6-MP
Authors:Alessandra Aldinucci  Tiziana Biagioli  Cinzia Manuelli  Anna Maria Repice  Luca Massacesi  Clara Ballerini
Affiliation:1. Institute of Rheumatology, Prague, Czech Republic;2. Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, General University Hospital in Prague, Prague, Czech Republic;3. Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
Abstract:Azathioprine (Aza), 6-Mercaptopurine (6-MP) and 6-Thioguanine (6-TG) are thiopurine drugs widely used as immunosuppressants/anti-inflammatory agents in organ transplantation and chemotherapy. Aza is well tolerated and effective in modifying the course of MS. Here we investigated the action of 6-MP on human dendritic cells (DCs). We described for the first time that 6-MP impairs in vitro differentiation of DCs, has an inhibitory effect during DC activation processes inducing a functionally less immunogenic phenotype. Moreover, 6-MP significantly reduces DC IL-23 production and CCR7 expression, at the same time induces IL-10 augmentation. All these findings add a novel action mechanism in Aza immune modulation.
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