PMID- 19415548 OWN - NLM STAT- MEDLINE DCOM- 20090722 LR - 20090505 IS - 1521-0499 (Electronic) IS - 0190-2148 (Linking) VI - 35 IP - 4 DP - 2009 May TI - Lipopolysaccharide stimulation of dendritic cells induces interleukin-10 producing allergen-specific T cells in vitro but fails to prevent allergic airway disease. PG - 307-23 LID - 10.1080/01902140802709460 [doi] AB - Dendritic cells (DCs) play an important role in directing naive T cells towards a Th1/Th2 or regulatory T cells (Treg) cell phenotype. In this context, interleukin (IL)-10 has been shown to exhibit immune regulatory capacities. The aim of this study was to delineate the influence of high-IL-10-producing DCs on DC-T-cell interactions in inhibiting allergen-induced airway inflammation and hyperreactivity in a murine model of allergic airway disease. Bone marrow-derived dendritic cells (BMDCs) were generated from hemopoietic progenitors by culture with granulocyte-macrophage colony-stimulating factor (GM-CSF), and stimulated with ovalbumin (OVA) +/- lipopolysaccharide (LPS). The effects of ovalbumin-pulsed BMDCs on cytokine production by allergen-specific naive T cells were studied in vitro. The development of airway inflammation in Balb/c mice was determined after intranasal administration of BMDCs in vivo. LPS stimulation of BMDCs strongly enhanced IL-10 production. Coculture of LPS-modulated DCs exhibiting increased IL-10 production with allergen-specific naive T cells reduced the production of interferon (IFN)-gamma and IL-5, but enhanced the production of IL-10. After blockade with anti-IL-10 plus anti-IL-10-receptor antibodies, the level of IFN-gamma and IL-5 production by cocultured T cells was restored, underlining the regulatory function of IL-10. Intranasal administration of high-IL-10-producing LPS-stimulated, OVA-primed BMDCs prior to repetitive airway allergen challenges resulted in an even enhanced airway inflammation. These data demonstrate that increased IL-10 production by DCs may be a critical element for T-cell activation and differentiation in the context of allergen-induced immune responses in vitro. However, this DC modulation did not translate into suppression of allergic airway disease in vivo. FAU - Ahrens, Birgit AU - Ahrens B AD - Department of Pediatric Pneumology and Immunology, Charite, University Medicine Berlin, Germany. birgit.ahrens@charite.de FAU - Freund, Tobias AU - Freund T FAU - Rha, Ro-Dug AU - Rha RD FAU - Dittrich, Anna-Maria AU - Dittrich AM FAU - Quarcoo, David AU - Quarcoo D FAU - Hutloff, Andreas AU - Hutloff A FAU - Hamelmann, Eckard AU - Hamelmann E LA - eng PT - Journal Article PL - England TA - Exp Lung Res JT - Experimental lung research JID - 8004944 RN - 0 (Allergens) RN - 0 (Interleukin-5) RN - 0 (Lipopolysaccharides) RN - 130068-27-8 (Interleukin-10) RN - 82115-62-6 (Interferon-gamma) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Allergens/*immunology MH - Animals MH - Asthma/*immunology MH - Cells, Cultured MH - Dendritic Cells/drug effects/*immunology MH - Female MH - Interferon-gamma/biosynthesis MH - Interleukin-10/*biosynthesis MH - Interleukin-5/biosynthesis MH - Lipopolysaccharides/pharmacology MH - Mice MH - Mice, Inbred BALB C MH - Ovalbumin/immunology MH - T-Lymphocytes/*immunology EDAT- 2009/05/06 09:00 MHDA- 2009/07/23 09:00 CRDT- 2009/05/06 09:00 PHST- 2009/05/06 09:00 [entrez] PHST- 2009/05/06 09:00 [pubmed] PHST- 2009/07/23 09:00 [medline] AID - 910943457 [pii] AID - 10.1080/01902140802709460 [doi] PST - ppublish SO - Exp Lung Res. 2009 May;35(4):307-23. doi: 10.1080/01902140802709460.