title: CD90(+) human dermal stromal cells are potent inducers of FoxP3(+) regulatory T cells.
abstract: The skin has to effectively combat external attacks, while maintaining skin immune homeostasis under steady-state conditions. To fulfill these challenging tasks, the dermis harbors a variety of heterogeneous cell types that are able to suppress T-cell proliferation similar to bone marrow mesenchymal stromal cells. Here we show that plastic-adherent, human dermal cells induce FoxP3 expression in TCR-complex-stimulated CD25(-)CD4(+)CD45RA(+) T cells in the absence of CD28 co-ligation in a cell-contact-dependent manner. These FoxP3(+) T cells reveal an effective suppressive capacity in vitro. Moreover, we found that the vast majority of CD90(+) dermal cells are perivascularly located and generate a significantly higher percentage of regulatory T cells compared with cells expressing markers such as CD271 in vitro. Importantly, we further demonstrate that plastic-adherent dermal cells are also able to differentiate toward the endothelial lineage. Our data show that human skin harbors specific cell types with immunosuppressive potential, which are located in close vicinity to their likely operational area and provide evidence for a CD28-independent regulatory mechanism. Further, the differentiation potential into endothelial cells suggests the existence of a tissue-resident cell pool for vessel regeneration. These findings might have important implications for the clinical use of allogeneic dermal cells to rebuild an imbalanced human skin immune homeostasis.
authors: Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases (DIAID), Laboratory of Cellular and Molecular Immunobiology of the Skin, Medical University of Vienna, Vienna, Austria; Current address: Molecular Immunology Unit, Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors: Karin
authors: K
authors: Pfisterer
authors: Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
authors: Karoline M
authors: KM
authors: Lipnik
authors: Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria.
authors: Erhard
authors: E
authors: Hofer
authors: Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases (DIAID), Laboratory of Cellular and Molecular Immunobiology of the Skin, Medical University of Vienna, Vienna, Austria. Electronic address: adelheid.elbe-buerger@meduniwien.ac.at.
authors: Adelheid
authors: A
authors: Elbe-Bürger
mesh_terms: D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation; D018920:Coculture Techniques; D020405:Dermis / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D052816:Foreskin / Q000166:cytology; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D057809:HEK293 Cells; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D061251:Primary Cell Culture; D017154:Stromal Cells / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018800:Thy-1 Antigens / Q000276:immunology* / Q000378:metabolism
chemical_list: D018106:CD28 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018800:Thy-1 Antigens