Titre
Interleukin-35-Producing CD8α(+) Dendritic Cells Acquire a Tolerogenic State and Regulate T Cell Function.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Haller, S.
Auteure/Auteur
Duval, A.
Auteure/Auteur
Migliorini, R.
Auteure/Auteur
Stevanin, M.
Auteure/Auteur
Mack, V.
Auteure/Auteur
Acha-Orbea, H.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1664-3224
Statut éditorial
Publié
Date de publication
2017
Volume
8
Première page
98
Peer-reviewed
Oui
Langue
anglais
Résumé
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.
PID Serval
serval:BIB_E7A621997879
PMID
Open Access
Oui
Date de création
2017-03-07T19:42:26.070Z
Date de création dans IRIS
2025-05-21T07:03:00Z
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Nom
fimmu-08-00098.pdf
Version du manuscrit
published
Taille
6.66 MB
Format
Adobe PDF
PID Serval
serval:BIB_E7A621997879.P001
URN
urn:nbn:ch:serval-BIB_E7A6219978793
Somme de contrôle
(MD5):94cef4c15735d36604bab8f70e86ed0b