title: Differential capacity of human skin dendritic cells to polarize CD4+ T cells into IL-17, IL-21 and IL-22 producing cells.
abstract: 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.
authors.affiliation: Université de Lyon, Hôpital E. Herriot, Lyon, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Penel-Sotirakis
authors.forename: Elise
authors.initials: E
authors.lastname: Simonazzi
authors.forename: Josette
authors.initials: J
authors.lastname: Péguet-Navarro
authors.forename: Aurore
authors.initials: A
authors.lastname: Rozières
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D060887:B7 Antigens / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects / Q000276:immunology; D018920:Coculture Techniques; D020405:Dermis / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007156:Immunologic Memory; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis* / Q000276:immunology; D007801:Langerhans Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D000097043:Interleukin-22; D000098546:Interleukin-21
chemical_list: D015703:Antigens, CD; D060887:B7 Antigens; D060945:Inducible T-Cell Co-Stimulator Ligand; D020381:Interleukin-17; D007378:Interleukins; D016212:Transforming Growth Factor beta; D000097043:Interleukin-22; D000098546:Interleukin-21; C498514:ICOSLG protein, human