%0 Journal Article
%T Differential Capacity of Human Skin Dendritic Cells to Polarize CD4+T Cells into IL-17, IL-21 and IL-22 Producing Cells
%A Karine Penel-Sotirakis
%A Elise Simonazzi
%A Josette P¨¦guet-Navarro
%A Aurore Rozi¨¨res
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0045680
%X 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 na£¿ve 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 na£¿ve 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-¦Ã, 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-¦Â 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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0045680