Ambivalent effects of dendritic cells displaying prostaglandin E2‐induced indoleamine 2,3‐dioxygenase

Prostaglandin E2 (PGE2), an abundantly produced lipid messenger in mammalian organisms, has been attributed to possess potent albeit ambivalent immunological functions. Recently, PGE2 has been reported to stimulate the commonly believed immunosuppressive indoleamine 2,3‐dioxygenase (IDO) pathway in...

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Bibliographic Details
Published in:European journal of immunology 2012-05, Vol.42 (5), p.1117-1128
Main Authors: Lanzinger, Margit, Jürgens, Birgit, Hainz, Ursula, Dillinger, Barbara, Raberger, Julia, Fuchs, Dietmar, Heitger, Andreas
Format: Article
Language:English
Subjects:
Cell Differentiation
Cells, Cultured
Coculture Techniques
Cytokines - biosynthesis
Cytokines - immunology
Dendritic cells
Dendritic Cells - drug effects
Dendritic Cells - enzymology
Dendritic Cells - immunology
Dinoprostone - immunology
Dinoprostone - pharmacology
Human dendritic cells
Humans
IL‐23
Immunosuppression
Indoleamine 2,3-dioxygenase (IDO)
Indoleamine-Pyrrole 2,3,-Dioxygenase - antagonists & inhibitors
Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism
Lymphocyte Activation - immunology
Lymphocytes
Prostaglandin E2
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
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Summary:Prostaglandin E2 (PGE2), an abundantly produced lipid messenger in mammalian organisms, has been attributed to possess potent albeit ambivalent immunological functions. Recently, PGE2 has been reported to stimulate the commonly believed immunosuppressive indoleamine 2,3‐dioxygenase (IDO) pathway in human dendritic cells (DCs), but without promoting DC immunosuppressive activity. Here, we report that PGE2 used as a DC maturation agent apparently has more diverse functions. PGE2‐matured DCs acquired powerful IDO activity, which was sustained even after removing PGE2. These IDO‐competent DCs were able to stimulate allogeneic T‐cell proliferation, but achieved inhibitory activity as their content in DC/T‐cell co‐cultures increased. The DC inhibitory activity was reversed upon blockade of IDO activity, confirming that the suppressive effect was in fact mediated by IDO and occurred in a dose‐dependent fashion. IDO‐mediated T‐cell suppression was restored upon re‐stimulation of T cells in the absence of IDO activity, confirming its reversibility. T cells stimulated by PGE2‐matured IDO‐competent DCs were sensitized to produce multiple cytokines, comprising Th1, Th2, and Th17 phenotypes. Collectively, these data suggest that T cells stimulated by PGE2‐matured DCs are not terminally differentiated and their ultimate type of response may be formed by microenvironmental conditions.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201141765