Modulating Dendritic Cells (DC) From Immunogenic to Tolerogenic Responses: A Novel Mechanism of AZA/6-MP

J Neuroimmunol. 2010 Jan 25;218(1-2):28-35. doi: 10.1016/j.jneuroim.2009.11.001. Epub 2009 Nov 24.

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.

MeSH terms

  • Adult
  • Azathioprine / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Female
  • Humans
  • Immune Tolerance / drug effects*
  • Immunosuppressive Agents / pharmacology*
  • Lymphocyte Culture Test, Mixed
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Receptors, CCR7 / biosynthesis
  • Receptors, CCR7 / drug effects

Substances

  • CCR7 protein, human
  • Immunosuppressive Agents
  • Receptors, CCR7
  • Azathioprine