Interleukin-35-Producing CD8α(+) Dendritic Cells Acquire a Tolerogenic State and Regulate T Cell Function.

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Version: Final published version
Serval ID
serval:BIB_E7A621997879
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Interleukin-35-Producing CD8α(+) Dendritic Cells Acquire a Tolerogenic State and Regulate T Cell Function.
Journal
Frontiers in Immunology
Author(s)
Haller S., Duval A., Migliorini R., Stevanin M., Mack V., Acha-Orbea H.
ISSN-L
1664-3224
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
8
Pages
98
Language
english
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 function in vitro and also in 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.

Keywords
dendritic cells, interleukin-35, immune tolerance, EAE, mouse
Pubmed
Web of science
Open Access
Yes
Create date
07/03/2017 20:42
Last modification date
20/08/2019 16:10
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