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Dendritic cells as pharmacological targets for the generation of regulatory immunosuppressive effectors. New implications for allo-transplantation.

Abstract：

:Dendritic cells (DCs) play a central role in the establishment of tolerance/immunity, because they activate naïve T cells (TCs). Therefore, the pharmacological modulation of DCs has become a major field of interest in immunology. A large body of literature has arisen from the studies of DC biology during immunosuppressive drug treatment. Immunosuppressive drugs have improved the therapeutic management of allograft organ transplantation and autoimmune diseases, significantly. There is now strong evidence that, DCs might be the key for antigen specific tolerance induction. Recently, the existence of a population of DCs that migrate to the regional lymph node in the steady state has been identified. Such steady state immature migrating DCs are loaded with tissue antigens and deliver self-antigens towards secondary lymphatic organs and might educate TCs towards self-tolerance. Latest experimental data from rodent solid organ allo-transplantation supports the idea, that DCs might even become regulatory DCs towards foreign antigen specific tolerance induction. Apparently, regulatory donor DCs invade host secondary lymphatic organs where they might eventually educate host TCs towards foreign antigen specific tolerance. Seemingly, it depends on the DC maturation state whether pharmacologically modulated DCs induce antigen specific long-term tolerance in allo-transplantation solid organ transplantation. Several authors reported a positive self-limiting feedback loop between tolerogenic DCs and allo-specific regulatory TCs. Thus, the DC-TC network appears as an exceptionally good target for pharmacological manipulations. Here we review how immunosuppressive agents interfere with DC maturation, migration and homeostasis. We are developing a rational to select different drugs for the generation of regulatory DCs, for allo-transplantation clinical settings.

journal_name

Curr Med Chem

journal_title

Current medicinal chemistry

authors

Schlichting CL,Schareck WD,Nickel T,Weis M

doi

10.2174/0929867054546627

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

1921-30

issue

eissn

0929-8673

issn

1875-533X

journal_volume

pub_type

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Dendritic cells as pharmacological targets for the generation of regulatory immunosuppressive effectors. New implications for allo-transplantation.