PMID- 16310277 OWN - NLM STAT- MEDLINE DCOM- 20060720 LR - 20181201 IS - 0168-8278 (Print) IS - 0168-8278 (Linking) VI - 44 IP - 3 DP - 2006 Mar TI - Hepatic environment elicits monocyte differentiation into a dendritic cell subset directing Th2 response. PG - 552-9 AB - BACKGROUND/AIMS: Dendritic cells (DCs), which play a critical role during immune response, could present alternative differentiation patterns depending on tissue microenvironment. Our aim was to examine the influence of hepatic microenvironment on human monocyte differentiation into DCs. METHODS: Cytology, immunophenotyping, cytokine production and T-cell activation were analyzed in DCs differentiated from human monocytes co-cultured with rat liver epithelial cells (RLEC) or human cells from various tissue origins and compared to control DCs obtained on plastic with GM-CSF/IL-4. RESULTS: RLEC environment promotes DC differentiation in the presence of IL-4 without GM-CSF. These DCs evidence similar expression of MHC-II, co-stimulatory and adhesion molecules than control DCs, but distinct lineage markers defining a CD11c+/CD14+/CD123+ DC subset. This phenotype is common to DCs from RLEC and human liver environment and differs from that obtained with skin or intestine environments. Functionally, they produce IL-10 but not IL-12p70 and favor IL-4/IL-10 secretion by T-cells rather than IFN-gamma. CONCLUSIONS: Our results confirm that tissue niches modulate DC differentiation and demonstrate that hepatic environment influences monocyte differentiation into a DC subset directing Th2 response, a key data for understanding the specialized immune response in liver. They also make RLEC co-culture system useful for studying liver DC functions. FAU - Cabillic, Florian AU - Cabillic F AD - INSERM U522, IFR140, Universite de Rennes 1, Hopital Pontchaillou, 35033 Rennes, France. FAU - Rougier, Nathalie AU - Rougier N FAU - Basset, Christelle AU - Basset C FAU - Lecouillard, Isabelle AU - Lecouillard I FAU - Quelvennec, Erwann AU - Quelvennec E FAU - Toujas, Louis AU - Toujas L FAU - Guguen-Guillouzo, Christiane AU - Guguen-Guillouzo C FAU - Corlu, Anne AU - Corlu A LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050915 PL - Netherlands TA - J Hepatol JT - Journal of hepatology JID - 8503886 RN - 130068-27-8 (Interleukin-10) RN - 207137-56-2 (Interleukin-4) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - *Cell Differentiation MH - Cells, Cultured MH - Dendritic Cells/*cytology/drug effects/metabolism MH - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology MH - Humans MH - *Immunity, Cellular MH - In Vitro Techniques MH - Interleukin-10/metabolism MH - Interleukin-4/pharmacology MH - Liver/cytology/*immunology/metabolism MH - Monocytes/*cytology/drug effects/metabolism MH - Phenotype MH - Rats MH - Th2 Cells/cytology/*immunology/metabolism EDAT- 2005/11/29 09:00 MHDA- 2006/07/21 09:00 CRDT- 2005/11/29 09:00 PHST- 2005/03/18 00:00 [received] PHST- 2005/07/05 00:00 [revised] PHST- 2005/08/02 00:00 [accepted] PHST- 2005/11/29 09:00 [pubmed] PHST- 2006/07/21 09:00 [medline] PHST- 2005/11/29 09:00 [entrez] AID - S0168-8278(05)00561-1 [pii] AID - 10.1016/j.jhep.2005.08.010 [doi] PST - ppublish SO - J Hepatol. 2006 Mar;44(3):552-9. doi: 10.1016/j.jhep.2005.08.010. Epub 2005 Sep 15.