Hepatic environment elicits monocyte differentiation into a dendritic cell subset directing Th2 response.
OBJECTIVE
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.
Cabillic
Florian
F
INSERM U522, IFR140, Université de Rennes 1, Hôpital Pontchaillou, 35033 Rennes, France.
Rougier
Nathalie
N
Basset
Christelle
C
Lecouillard
Isabelle
I
Quelvennec
Erwann
E
Toujas
Louis
L
Guguen-Guillouzo
Christiane
C
Corlu
Anne
A
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D016753:Interleukin-10; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor