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

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2017

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info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2017.00098

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info:eu-repo/semantics/altIdentifier/pmid/28228759

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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_E7A6219978793

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S. Haller et al., « Interleukin-35-Producing CD8α(+) Dendritic Cells Acquire a Tolerogenic State and Regulate T Cell Function. », Serveur académique Lausannois, ID : 10.3389/fimmu.2017.00098


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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.

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