title: Fibroblasts support migration of monocyte-derived dendritic cells by secretion of PGE2 and MMP-1.
abstract: The outcome of a cutaneous immune response is critically dependent upon the ability of dendritic cells (DC) to migrate from skin to the draining lymph nodes - a process that is influenced by the cutaneous tissue microenvironment. Here, the role of fibroblasts - a major component of the dermal microenvironment - on the migratory capacity of monocyte-derived DC (MoDC) was investigated in a 3D collagen I matrix. Indeed, dermal fibroblasts supported the migration of pre-activated MoDC through a 3D collagen I matrix. Activation of human MoDC resulted in the release of TNFα and IL-1β that in turn stimulated MMP-1 (human collagenase) and PGE2 secretion by human dermal fibroblasts. Transmigration assays confirmed the importance of fibroblast-derived MMP-1 and PGE2 for the migration of MoDC through a 3D collagen I matrix. Finally, in mice initiation of inflammation by induction of an irritant contact dermatitis or a psoriasis-like skin inflammation, the expression of the PGE2 generating cox-2 and the mouse collagen I degrading enzyme matrix metalloproteinases (MMP)-13 was strongly up-regulated. Our study indicates that MoDC are able to instruct dermal fibroblasts resulting in enhanced migratory capability of MoDC, thus highlighting the role of a crosstalk of DC with their stromal microenvironment for the control of cutaneous immune responses.
authors: Department of Dermatology, Venerology and Allergology, Medical Faculty of Leipzig University, Leipzig, Germany.
authors: Anja
authors: A
authors: Saalbach
authors: Department of Dermatology, Venerology and Allergology, Medical Faculty of Leipzig University, Leipzig, Germany.
authors: Tobias
authors: T
authors: Janik
authors: Department of Dermatology, Venerology and Allergology, Medical Faculty of Leipzig University, Leipzig, Germany.
authors: Matthias
authors: M
authors: Busch
authors: Department of Dermatology, Venerology and Allergology, Medical Faculty of Leipzig University, Leipzig, Germany.
authors: Diana
authors: D
authors: Herbert
authors: Department of Dermatology, Venerology and Allergology, Medical Faculty of Leipzig University, Leipzig, Germany.
authors: Ulf
authors: U
authors: Anderegg
authors: Department of Dermatology, Venerology and Allergology, Medical Faculty of Leipzig University, Leipzig, Germany.
authors: Jan C
authors: JC
authors: Simon
mesh_terms: D000634:Aminoquinolines / Q000633:toxicity; D000818:Animals; D018929:Cell Culture Techniques; D002465:Cell Movement; D002478:Cells, Cultured; D060833:Cellular Microenvironment / Q000502:physiology*; D024042:Collagen Type I; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology*; D003877:Dermatitis, Contact / Q000209:etiology / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004790:Enzyme Induction; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D000077271:Imiquimod; D007509:Irritants / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D010853:Picryl Chloride / Q000633:toxicity; D011565:Psoriasis / Q000139:chemically induced / Q000378:metabolism; D017154:Stromal Cells / Q000502:physiology
chemical_list: D000634:Aminoquinolines; D024042:Collagen Type I; D016207:Cytokines; D007509:Irritants; D008070:Lipopolysaccharides; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D053509:Matrix Metalloproteinase 13; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; D015232:Dinoprostone; D000077271:Imiquimod; D010853:Picryl Chloride
keywords: dendritic cell; dermal microenvironment; fibroblast; migration