Differential capacity of human skin dendritic cells to polarize CD4+ T cells into IL-17, IL-21 and IL-22 producing cells

• Published in: PloS one Vol. 7; no. 11; p. e45680
• Main Authors: Penel-Sotirakis, Karine, Simonazzi, Elise, Péguet-Navarro, Josette, Rozières, Aurore
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30-11-2012; Public Library of Science (PLoS)
• Subjects: Antibiotics; Antigens, CD - genetics; Antigens, CD - immunology; B7 antigen; B7 Antigens - genetics; B7 Antigens - immunology; Biology; CD14 antigen; CD1c antigen; CD28 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell Communication - drug effects; Cell Differentiation - drug effects; Cell Lineage - drug effects; Cell Lineage - immunology; Coculture Techniques; Cytokines; Dendritic cells; Dermis - cytology; Dermis - drug effects; Dermis - immunology; Disorders; Epidermal Cells; Epidermis - drug effects; Epidermis - immunology; Gene Expression Regulation - drug effects; Homeostasis; Humans; Immunologic Memory; Immunological memory; Inducible T-Cell Co-Stimulator Ligand - genetics; Inducible T-Cell Co-Stimulator Ligand - immunology; Inflammatory diseases; Interferon; Interleukin 17; Interleukin 21; Interleukin 22; Interleukin 4; Interleukin-17 - biosynthesis; Interleukin-17 - immunology; Interleukins - biosynthesis; Interleukins - immunology; Langerhans cells; Langerhans Cells - cytology; Langerhans Cells - drug effects; Langerhans Cells - immunology; Leukocyte migration; Ligands; Lymphocytes; Lymphocytes T; Medicine; Memory cells; Pathogenesis; Psoriasis; Signal Transduction - drug effects; Skin; Specialization; T cell receptors; Transforming Growth Factor beta - pharmacology; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0045680

Accumulating evidence suggests a contribution of T cell-derived IL-17, IL-21 and IL-22 cytokines in skin immune homeostasis as well as inflammatory disorders. Here, we analyzed whether the cytokine-producing T lymphocytes could be induced by the different subsets of human skin dendritic cells (DCs), i.e., epidermal Langerhans cells (LCs), dermal CD1c(+)CD14(-) and CD14(+) DCs (DDCs). DCs were purified following a 2-day migration from separated epidermal and dermal sheets and co-cultured with allogeneic T cells before cytokine secretion was explored. Results showed that no skin DCs could induce substantial IL-17 production by naïve CD4(+) or CD8(+)T lymphocytes whereas all of them could induce IL-17 production by memory T cells. In contrast, LCs and CD1c(+)CD14(-)DDCs were able to differentiate naïve CD4(+)T lymphocytes into IL-22 and IL-21-secreting cells, LCs being the most efficient in this process. Intracellular cytokine staining showed that the majority of IL-21 or IL-22 secreting CD4(+)T lymphocytes did not co-synthesized IFN-γ, IL-4 or IL-17. IL-21 and IL-22 production were dependent on the B7/CD28 co-stimulatory pathway and ICOS-L expression on skin LCs significantly reduced IL-21 level. Finally, we found that TGF-β strongly down-regulates both IL-21 and IL-22 secretion by allogeneic CD4(+) T cells. These results add new knowledge on the functional specialization of human skin DCs and might suggest new targets in the treatment of inflammatory skin disorders.