PMID- 21543643 OWN - NLM STAT- MEDLINE DCOM- 20111007 LR - 20121115 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 186 IP - 12 DP - 2011 Jun 15 TI - Identification of IDO-positive and IDO-negative human dendritic cells after activation by various proinflammatory stimuli. PG - 6701-9 LID - 10.4049/jimmunol.1003151 [doi] AB - Dendritic cells (DCs) can induce tolerance or immunity. We identified and characterized an IDO-expressing and an IDO-negative human DC population after stimulation by various proinflammatory stimuli. IDO expression was strongly dependent on the maturation status of the cells (CD83-positive cells only). The two DC subpopulations remained IDO positive and IDO negative, respectively, over a time period of at least 48 h. IDO enzyme activity of human DCs was highest during stimulation by strongly maturation-inducing TLR ligands such as highly purified LPS (TLR4 ligand) or polyriboinosinic-polyribocytidilic acid (TLR3 ligand); factors of the adaptive immune system such as IFN-gamma, a mixture of cytokines, and IFN-alpha had lesser stimulatory capacity for IDO induction and activity. After stimulation with CD40L, IDO-positive DCs expressed significantly increased levels of B7 family molecules such as CD40, CD80, CD86, ICOS ligand, as well as PD-L1 (B7-H1) and PD-L2 (B7-DC) compared with the IDO-negative DC subset. At the same time, the inhibitory receptors Ig-like transcripts 3 and 4 were significantly downregulated on IDO-positive cells. Functionally, IDO-positive DCs produced significantly more IL-1beta and IL-15 and less IL-10 and IL-6 than the IDO-negative subset after CD40L stimulation. These results show that IDO expression is associated with a distinctive phenotype and functional capacity in mature DCs. It seems likely that the IDO-positive DC subset possesses a regulatory function and might skew a T cell response toward tolerance. FAU - Von Bubnoff, Dagmar AU - Von Bubnoff D AD - Department of Dermatology and Allergy, Friedrich-Wilhelms-University of Bonn, 53105 Bonn, Germany. d.bubnoff@uni-bonn.de FAU - Scheler, Marina AU - Scheler M FAU - Wilms, Helene AU - Wilms H FAU - Fimmers, Rolf AU - Fimmers R FAU - Bieber, Thomas AU - Bieber T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110504 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase) RN - 0 (Interleukins) RN - 0 (Ligands) RN - 0 (Toll-Like Receptors) SB - IM MH - Cells, Cultured MH - Dendritic Cells/*enzymology MH - Humans MH - Immune Tolerance/immunology MH - Indoleamine-Pyrrole 2,3,-Dioxygenase/*analysis MH - Inflammation/*chemically induced MH - Interleukins/biosynthesis MH - Ligands MH - Phenotype MH - Toll-Like Receptors/agonists EDAT- 2011/05/06 06:00 MHDA- 2011/10/08 06:00 CRDT- 2011/05/06 06:00 PHST- 2011/05/06 06:00 [entrez] PHST- 2011/05/06 06:00 [pubmed] PHST- 2011/10/08 06:00 [medline] AID - jimmunol.1003151 [pii] AID - 10.4049/jimmunol.1003151 [doi] PST - ppublish SO - J Immunol. 2011 Jun 15;186(12):6701-9. doi: 10.4049/jimmunol.1003151. Epub 2011 May 4.