PMID- 28228759
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 8
DP  - 2017
TI  - Interleukin-35-Producing CD8alpha(+) Dendritic Cells Acquire a Tolerogenic State and 
      Regulate T Cell Function.
PG  - 98
LID - 10.3389/fimmu.2017.00098 [doi]
LID - 98
AB  - 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 CD8alpha(+) 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 CD8alpha(+) 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.
FAU - Haller, Sergio
AU  - Haller S
AD  - Department of Biochemistry, Center for Immunity and Infection Lausanne (CIIL), 
      University of Lausanne , Lausanne , Switzerland.
FAU - Duval, Anais
AU  - Duval A
AD  - Institut de Pharmacologie et de Biologie Structurale, Centre National de la 
      Recherche Scientifique (CNRS), Universite Paul Sabatier, Universite de Toulouse , 
      Toulouse , France.
FAU - Migliorini, Romain
AU  - Migliorini R
AD  - Department of Biochemistry, Center for Immunity and Infection Lausanne (CIIL), 
      University of Lausanne , Lausanne , Switzerland.
FAU - Stevanin, Mathias
AU  - Stevanin M
AD  - Department of Biochemistry, Center for Immunity and Infection Lausanne (CIIL), 
      University of Lausanne , Lausanne , Switzerland.
FAU - Mack, Vanessa
AU  - Mack V
AD  - Department of Biochemistry, Center for Immunity and Infection Lausanne (CIIL), 
      University of Lausanne , Lausanne , Switzerland.
FAU - Acha-Orbea, Hans
AU  - Acha-Orbea H
AD  - Department of Biochemistry, Center for Immunity and Infection Lausanne (CIIL), 
      University of Lausanne , Lausanne , Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20170208
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC5296329
OTO - NOTNLM
OT  - EAE
OT  - dendritic cells
OT  - immune tolerance
OT  - interleukin-35
OT  - mouse
EDAT- 2017/02/24 06:00
MHDA- 2017/02/24 06:01
PMCR- 2017/01/01
CRDT- 2017/02/24 06:00
PHST- 2016/09/30 00:00 [received]
PHST- 2017/01/19 00:00 [accepted]
PHST- 2017/02/24 06:00 [entrez]
PHST- 2017/02/24 06:00 [pubmed]
PHST- 2017/02/24 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2017.00098 [doi]
PST - epublish
SO  - Front Immunol. 2017 Feb 8;8:98. doi: 10.3389/fimmu.2017.00098. eCollection 2017.