Differential Capacity of Human Skin Dendritic Cells to Polarize CD4.sup.+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: Public Library of Science 30-11-2012
• Subjects: Analysis; Cytokines; Dendritic cells; Dermatologic agents; Skin; T cells; Transforming growth factors
• 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.sup.+ CD14.sup.- and CD14.sup.+ 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.sup.+ or CD8.sup.+ T lymphocytes whereas all of them could induce IL-17 production by memory T cells. In contrast, LCs and CD1c.sup.+ CD14.sup.- DDCs were able to differentiate naïve CD4.sup.+ 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.sup.+ T lymphocytes did not co-synthesized IFN-[gamma], 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-[beta] strongly down-regulates both IL-21 and IL-22 secretion by allogeneic CD4.sup.+ 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.