Abstract
The importance of microenvironment on dendritic cell (DC) function and development has been strongly established during the last two decades. Although DCs with general tolerogenic characteristics have been isolated and defined as a particular sub-population, it is predominantly their unequivocal biological plasticity, which allows for unparalleled responsiveness to environmental ques and shaping of their tolerogenic characteristics when interacting with tolerance-inducing biomolecules. Dendritic cells carry receptors for a great number of endogenous factors, which, after ligation, can importantly influence the development of their activation state. For this there is ample evidence merely by observation of DC characteristics isolated from various anatomical niches, e.g., the greater immunosuppressive potential of DCs isolated from intestine compared to conventional blood DCs. Endogenous biomolecules present in these environments most likely play a major role as a determinant of their phenotype and function. In this review, we will concisely summarize in what way various, tolerance-inducing endogenous factors influence DC biology, the development of their particular tolerogenic state and their subsequent actions in context of immune response inhibition and induction of regulatory T cells.
Highlights
Dendritic cells (DCs) comprise a heterogenous and specialized immune cell subset with the main role of sampling and presenting both endogenous and foreign antigens (Ags) to cells of the adaptive immune system
If one was to search for reason why Tolerogenic DCs (TolDCs) are much more efficient in inducing tolerogenic responses in comparison to immature DCs, it is the presence of elements of active tolerance-induction, which are expressed on TolDCs in an extensive manner
The context-specific role of IFN-γ was recently demonstrated by our group, where we investigated the effects of an IFN-γrich environment on the DC inhibitory phenotype
Summary
Dendritic cells (DCs) comprise a heterogenous and specialized immune cell subset with the main role of sampling and presenting both endogenous and foreign antigens (Ags) to cells of the adaptive immune system. If one was to search for reason why TolDCs are much more efficient in inducing tolerogenic responses in comparison to immature DCs, it is the presence of elements of active tolerance-induction (surface inhibitory molecules, immunosuppressive cytokines), which are expressed on TolDCs in an extensive manner. The tolerogenic function of DCs expressing IFN-γ-induced IDO can be seen in reduced T cell proliferation [31] and the induction of Tregs [32].
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