title: Interleukin-35-Producing CD8α+Dendritic Cells Acquire a Tolerogenic State and Regulate T Cell Function.
abstract: Dendritic cells (DCs) play a central role in shaping immunogenic as well as tolerogenic adaptive immune responses and thereby dictate the outcome of adaptive immunity. Here, we report the generation of a CD8α+DC line constitutively secreting the tolerogenic cytokine interleukin (IL)-35. IL-35 secretion led to impaired CD4+and CD8+T lymphocyte proliferation and interfered with their functionin vitroand alsoin vivo. IL-35 was furthermore found to induce a tolerogenic phenotype on CD8α+DCs, characterized by the upregulation of CD11b, downregulation of MHC class II, a reduced costimulatory potential as well as production of the immunomodulatory molecule IL-10. Vaccination of mice with IL-35-expressing DCs promoted tumor growth and reduced the severity of autoimmune encephalitis not only in a preventive but also after induction of encephalitogenic T cells. The reduction in experimental autoimmune encephalitis severity was significantly more pronounced when antigen-pulsed IL-35+DCs were used. These findings suggest a new, indirect effector mechanism by which IL-35-responding antigen-presenting cells contribute to immune tolerance. Furthermore, IL-35-transfected DCs may be a promising approach for immunotherapy in the context of autoimmune diseases.
authors.affiliation: Department of Biochemistry, Center for Immunity and Infection Lausanne (CIIL), University of Lausanne , Lausanne , Switzerland.
authors.forename: Sergio
authors.initials: S
authors.lastname: Haller
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier, Université de Toulouse , Toulouse , France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Duval
authors.affiliation: Department of Biochemistry, Center for Immunity and Infection Lausanne (CIIL), University of Lausanne , Lausanne , Switzerland.
authors.forename: Romain
authors.initials: R
authors.lastname: Migliorini
authors.affiliation: Department of Biochemistry, Center for Immunity and Infection Lausanne (CIIL), University of Lausanne , Lausanne , Switzerland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Stevanin
authors.affiliation: Department of Biochemistry, Center for Immunity and Infection Lausanne (CIIL), University of Lausanne , Lausanne , Switzerland.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Mack
authors.affiliation: Department of Biochemistry, Center for Immunity and Infection Lausanne (CIIL), University of Lausanne , Lausanne , Switzerland.
authors.forename: Hans
authors.initials: H
authors.lastname: Acha-Orbea
keywords: EAE; dendritic cells; immune tolerance; interleukin-35; mouse