title: Differential capability of human cutaneous dendritic cell subsets to initiate Th17 responses.
abstract: Human skin-migratory dendritic cells (DCs) have the ability to prime and bias Th1 and Th2 CD4+ T lymphocytes. However, whether human cutaneous DCs are capable of initiating proinflammatory Th17 responses remains undetermined. We report that skin-migratory DCs stimulate allogeneic naive CD4+ T cells that differentiate simultaneously into two distinct effector Th17 and Th1 populations capable of homing to the skin, where they induce severe cutaneous damage. Skin-migratory Langerhans cells (smiLCs) were the main cutaneous DC subset capable of inducing Th17 responses dependent on the combined effects of IL-15 and stabilized IL-6, which resulted in IL-6 trans-signaling of naive CD4+ T cells. Different from smiLCs, purified skin-migratory dermal DCs did not synthesize IL-15 and were unable to bias Th17 responses. Nevertheless, these dermal DCs were capable of differentiating Th17 cells in mixed leukocyte cultures supplemented with IL-15 and stabilized IL-6. Overall, our data demonstrate that human epidermal smiLCs induce Th17 responses by mechanisms different from those previously described and highlight the need to target clinical treatments based on these variations.
authors.affiliation: Department of Dermatology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Mathers
authors.forename: Brian M
authors.initials: BM
authors.lastname: Janelsins
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Rubin
authors.forename: Olga A
authors.initials: OA
authors.lastname: Tkacheva
authors.forename: William J
authors.initials: WJ
authors.lastname: Shufesky
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.forename: Adrian E
authors.initials: AE
authors.lastname: Morelli
authors.forename: Adriana T
authors.initials: AT
authors.lastname: Larregina
mesh_terms: D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D019409:Interleukin-15 / Q000096:biosynthesis / Q000502:physiology; D020381:Interleukin-17 / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism / Q000502:physiology; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D009924:Organ Culture Techniques; D015398:Signal Transduction / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D018836:Inflammation Mediators; D019409:Interleukin-15; D020381:Interleukin-17; D015850:Interleukin-6