PMID- 17594940 OWN - NLM STAT- MEDLINE DCOM- 20070926 LR - 20070801 IS - 1148-5493 (Print) IS - 1148-5493 (Linking) VI - 18 IP - 2 DP - 2007 Jun TI - Short-term lipopolysaccharide stimulation induces differentiation of murine bone marrow-derived dendritic cells into a tolerogenic phenotype. PG - 78-85 AB - Dendritic cells (DCs) are professional, antigen-presenting cells, which induce and regulate T cell reactivity. DCs are crucial in innate and adaptive immune responses, and are also involved in central and peripheral tolerance induction. Tolerance can be mediated by immature and semi-mature DCs expressing low levels of co-stimulator and major histocompatibility complex (MHC) molecules. The aim of this study was to investigate the ability of short-term lipopolysaccharide (LPS) stimulation to modulate the stage of differentiation of bone marrow-derived DCs. For this purpose, DCs obtained from DBA1/lacJ mice were stimulated for four (4hLPS/DCs) or 24 (24hLPS/DCs) hours with LPS, using DCs without stimulation (0hLPS/DCs) as a control. Flow cytometry analysis of 4hLPS/DCs showed intermediate CD40 and MHC class II expression, lower than that of 24hLPS/DCs (fully mature), and greater than that of 0hLPS/DCs (immature). A functional assay showed that 4hLPS/DCs displayed increased endocytotic ability compared to 24hLPS/DCs, indicating a semi-mature state. 4hLPS/DCs were greater producers of IL-10 protein and TGFbeta1 mRNA than 24hLPS/DCs and immature DCs, displaying a cytokine production pattern that is characteristic of tolerogenic DCs. An assay for antigen-presenting capacity demonstrated that 4hLPS/DCs induced secretion of IL-2 from an OTH4 T cell hybridoma, indicating a functional presenting activity. Finally, the tolerogenic phenotype of 4hLPS/DCs was demonstrated by their ability to interfere with the progression of bovine type II collagen (bII)-induced arthritis (CIA) when they were loaded with bCII antigen and injected into mice with established CIA. We conclude that the stimulation of murine bone marrow-derived DCs with LPS for four hours generates semi-mature DCs with tolerogenic capability. FAU - Salazar, Lorena AU - Salazar L AD - Programa Disciplinario de Inmunologia, Instituto de Ciencias Biomedicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile. FAU - Aravena, Octavio AU - Aravena O FAU - Contreras-Levicoy, Juan AU - Contreras-Levicoy J FAU - Pesce, Barbara AU - Pesce B FAU - Catalan, Diego AU - Catalan D FAU - Zuniga, Roberto AU - Zuniga R FAU - Iruretagoyena, Mirentxu AU - Iruretagoyena M FAU - Kalergis, Alexis M AU - Kalergis AM FAU - Aguillon, Juan C AU - Aguillon JC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070626 PL - France TA - Eur Cytokine Netw JT - European cytokine network JID - 9100879 RN - 0 (Lipopolysaccharides) RN - 0 (Transforming Growth Factor beta1) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Animals MH - Bone Marrow Cells/*cytology MH - Cell Differentiation MH - Cell Separation MH - Dendritic Cells/*cytology MH - Flow Cytometry MH - Interleukin-10/metabolism MH - Interleukin-12/metabolism MH - Lipopolysaccharides/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Inbred DBA MH - T-Lymphocytes/metabolism MH - Transforming Growth Factor beta1/metabolism EDAT- 2007/06/28 09:00 MHDA- 2007/09/27 09:00 CRDT- 2007/06/28 09:00 PHST- 2007/06/12 00:00 [accepted] PHST- 2007/06/28 09:00 [pubmed] PHST- 2007/09/27 09:00 [medline] PHST- 2007/06/28 09:00 [entrez] AID - ecn.2007.0089 [pii] AID - 10.1684/ecn.2007.0089 [doi] PST - ppublish SO - Eur Cytokine Netw. 2007 Jun;18(2):78-85. doi: 10.1684/ecn.2007.0089. Epub 2007 Jun 26.