Dermal fibroblasts induce maturation of dendritic cells.
To trigger an effective T cell-mediated immune response in the skin, cutaneous dendritic cells (DC) migrate into locally draining lymph nodes, where they present Ag to naive T cells. Little is known about the interaction of DC with the various cellular microenvironments they encounter during their migration from the skin to lymphoid tissues. In this study, we show that human DC generated from peripheral blood monocytes specifically interact with human dermal fibroblasts via the interaction of beta(2) integrins on DC with Thy-1 (CD90) and ICAM-1 on fibroblasts. This induced the phenotypic maturation of DC reflected by expression of CD83, CD86, CD80, and HLA-DR in a TNF-alpha- and ICAM-1-dependent manner. Moreover, fibroblast-matured DC potently induced T cell activation reflected by CD25 expression and enhanced T cell proliferation. Together these data demonstrate that dermal fibroblasts that DC can encounter during their trafficking from skin to lymph node can act as potent regulators of DC differentiation and function, and thus may actively participate in the regulation and outcome of DC-driven cutaneous immune responses.
Saalbach
Anja
A
Department of Dermatology, Venerology, and Allergology, Medical Faculty of Leipzig University, Leipzig, Germany. Anja.Saalbach@medizin.uni-leipzig.de
Klein
Claudia
C
Sleeman
Jonathan
J
Sack
Ulrich
U
Kauer
Friederike
F
Gebhardt
Carl
C
Averbeck
Marco
M
Anderegg
Ulf
U
Simon
Jan C
JC
D002450:Cell Communication; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008213:Lymphocyte Activation; D012867:Skin / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D018800:Thy-1 Antigens / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D018800:Thy-1 Antigens; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1