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Title (Primary) Human fibroblasts support the expansion of IL-17-producing T cells via up-regulation of IL-23 production by dendritic cells
Author Schirmer, C.; Klein, C.; von Bergen, M.; Simon, J.-C.; Saalbach, A.;
Journal Blood
Year 2010
Department PROTEOM;
Volume 116
Issue 10
Language englisch;
Abstract The initiation of immune responses is associated with the maturation of dendritic cells (DCs) and their migration to draining lymph nodes. En route activated DCs encounter cells of the tissue microenvironment, such as fibroblasts. Because we have shown that DCs interact with fibroblasts during immune responses, we studied the impact of skin fibroblasts on human monocyte-derived DC function and subsequent human T-cell (TC) differentiation. We show that fibroblasts support interleukin-23 (IL-23) secretion from DCs preactivated by lipopolysaccharide (DCact) compared with lipopolysaccharide-activated DCs alone. The underlying complex feedback-loop mechanism involves IL-1ß/tumor necrosis factor- (from DCact), which stimulate fibroblasts prostaglandin E2 production. Prostaglandin E2, in turn, acts on DCact and increases their IL-23 release. Furthermore, fibroblast-stimulated DCact are far superior to DCact alone, in promoting the expansion of Th17 cells in a Cox-2-, IL-23-dependent manner. Using CD4+CD45RO+ memory TCs and CD4+CD45RA+ naive TCs, we showed that fibroblasts induce a phenotype of DCact that promotes the expansion of Th17 cells. Moreover, in psoriasis, a prototypic immune response in which the importance of IL-23/Th17 is known, high expression of Cox-2 in fibroblasts was observed. In conclusion, skin fibroblasts are involved in regulation of IL-23 production in DCs and, as a result, of Th17 expansion.
ID 10469
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=10469
Schirmer, C., Klein, C., von Bergen, M., Simon, J.-C., Saalbach, A. (2010):
Human fibroblasts support the expansion of IL-17-producing T cells via up-regulation of IL-23 production by dendritic cells
Blood 116 (10), 1715 - 1725