PMID- 33679743
OWN - NLM
STAT- MEDLINE
DCOM- 20210702
LR  - 20221207
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - IL10- and IL35-Secreting MutuDC Lines Act in Cooperation to Inhibit Memory T Cell 
      Activation Through LAG-3 Expression.
PG  - 607315
LID - 10.3389/fimmu.2021.607315 [doi]
LID - 607315
AB  - Dendritic cells (DCs) are professional antigen-presenting cells involved in the 
      initiation of immune responses. We generated a tolerogenic DC (tolDC) line that 
      constitutively secretes interleukin-10 (IL10-DCs), expressed lower levels of 
      co-stimulatory and MHCII molecules upon stimulation, and induced antigen-specific 
      proliferation of T cells. Vaccination with IL10-DCs combined with another tolDC 
      line that secretes IL-35, reduced antigen-specific local inflammation in a 
      delayed-type hypersensitivity assay independently on regulatory T cell 
      differentiation. In an autoimmune model of rheumatoid arthritis, vaccination with 
      the combined tolDCs after the onset of the disease impaired disease development 
      and promoted recovery of mice. After stable memory was established, the tolDCs 
      promoted CD4 downregulation and induced lymphocyte activation gene 3 (LAG-3) 
      expression in reactivated memory T cells, reducing T cell activation. Taken 
      together, our findings indicate the benefits of combining anti-inflammatory 
      cytokines in an antigen-specific context to treat excessive inflammation when 
      memory is already established.
CI  - Copyright (c) 2021 Koga, Engel, Pigni, Lavanchy, Stevanin, Laversenne, Schneider 
      and Acha-Orbea.
FAU - Koga, Marianna M
AU  - Koga MM
AD  - Department of Biochemistry, Center of Immunity and Infection Lausanne, University 
      of Lausanne, Lausanne, Switzerland.
FAU - Engel, Adrien
AU  - Engel A
AD  - Department of Biochemistry, Center of Immunity and Infection Lausanne, University 
      of Lausanne, Lausanne, Switzerland.
FAU - Pigni, Matteo
AU  - Pigni M
AD  - Department of Biochemistry, Center of Immunity and Infection Lausanne, University 
      of Lausanne, Lausanne, Switzerland.
FAU - Lavanchy, Christine
AU  - Lavanchy C
AD  - Department of Biochemistry, Center of Immunity and Infection Lausanne, University 
      of Lausanne, Lausanne, Switzerland.
FAU - Stevanin, Mathias
AU  - Stevanin M
AD  - Department of Biochemistry, Center of Immunity and Infection Lausanne, University 
      of Lausanne, Lausanne, Switzerland.
FAU - Laversenne, Vanessa
AU  - Laversenne V
AD  - Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, Lausanne, 
      Switzerland.
FAU - Schneider, Bernard L
AU  - Schneider BL
AD  - Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, Lausanne, 
      Switzerland.
AD  - Bertarelli Platform for Gene Therapy, Ecole Polytechnique Federale de Lausanne, 
      Geneva, Switzerland.
FAU - Acha-Orbea, Hans
AU  - Acha-Orbea H
AD  - Department of Biochemistry, Center of Immunity and Infection Lausanne, University 
      of Lausanne, Lausanne, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210217
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antigens, CD)
RN  - 0 (Cytokines)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Il12a protein, mouse)
RN  - 0 (Interleukin-12 Subunit p35)
RN  - 0 (Vaccines)
RN  - 130068-27-8 (Interleukin-10)
RN  - 0 (Lymphocyte Activation Gene 3 Protein)
RN  - 0 (Lag3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Antigens, CD/*genetics
MH  - Arthritis, Rheumatoid/immunology/metabolism/pathology/therapy
MH  - Cell Communication/immunology
MH  - Cell Line
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*immunology/*metabolism
MH  - Female
MH  - Gene Expression
MH  - Histocompatibility Antigens Class II/genetics/immunology
MH  - Immune Tolerance
MH  - *Immunologic Memory
MH  - Immunomodulation
MH  - Immunotherapy/methods
MH  - Interleukin-10/*biosynthesis
MH  - Interleukin-12 Subunit p35/*biosynthesis
MH  - Lymphocyte Activation/genetics/immunology
MH  - Mice
MH  - Mice, Knockout
MH  - T-Lymphocytes/*immunology/*metabolism
MH  - Vaccines/administration & dosage/immunology
MH  - Lymphocyte Activation Gene 3 Protein
PMC - PMC7925845
OTO - NOTNLM
OT  - IL-10
OT  - IL-35
OT  - LAG-3
OT  - dendritic cells
OT  - tolerogenic DCs
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/03/09 06:00
MHDA- 2021/07/03 06:00
PMCR- 2021/01/01
CRDT- 2021/03/08 05:50
PHST- 2020/09/16 00:00 [received]
PHST- 2021/01/26 00:00 [accepted]
PHST- 2021/03/08 05:50 [entrez]
PHST- 2021/03/09 06:00 [pubmed]
PHST- 2021/07/03 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.607315 [doi]
PST - epublish
SO  - Front Immunol. 2021 Feb 17;12:607315. doi: 10.3389/fimmu.2021.607315. eCollection 
      2021.