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.

journal_name

Exp Dermatol

journal_title

Experimental dermatology

authors

Saalbach A,Janik T,Busch M,Herbert D,Anderegg U,Simon JC

doi

10.1111/exd.12722

subject

Has Abstract

pub_date

2015-08-01 00:00:00

pages

598-604

issue

8

eissn

0906-6705

issn

1600-0625

journal_volume

24

pub_type

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