PMID- 27683749
OWN - NLM
STAT- MEDLINE
DCOM- 20170814
LR  - 20231213
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 197
IP  - 9
DP  - 2016 Nov 1
TI  - IL-10-Modulated Human Dendritic Cells for Clinical Use: Identification of a 
      Stable and Migratory Subset with Improved Tolerogenic Activity.
PG  - 3607-3617
AB  - Dendritic cells (DCs) are key regulators of protective immune responses and 
      tolerance to (self-)Ags. Therefore, the scientific rationale for the use of 
      tolerogenic DC therapy in the fields of allergies, autoimmunity, and 
      transplantation medicine is strong. In this study, we analyzed the tolerogenic 
      capacity of IL-10-modulated DC (IL-10DC) subpopulations to identify a DC subset 
      that combines potent immunosuppressive activities with valuable immune properties 
      for clinical implementation. IL-10DCs consist of two phenotypically distinct 
      subpopulations: CD83(high)CCR7(+) IL-10DCs and CD83(low)CCR7(-) IL-10DCs. 
      Suppressor assays with activated effector T cells revealed that CD4(+) regulatory 
      T cells generated by CD83(high) IL-10DCs (iTreg(+)) exhibited a significantly 
      higher suppressive capacity compared with CD4(+) regulatory T cells generated by 
      CD83(low) IL-10DCs (iTreg(-)). In this context, iTreg(+) displayed a more 
      activated phenotype (proliferation, cytokine production) compared with iTreg(-) 
      In contrast to CD83(low) IL-10DCs, CD83(high) IL-10DCs exerted a strong migratory 
      capacity toward the secondary lymphoid organ chemokine CCL21 and retained a 
      functionally stable phenotype under inflammatory conditions. In addition, 
      CD83(high) IL-10DCs expressed significantly higher levels of surface and soluble 
      CD25. Functional analysis demonstrated that IL-10DC-related soluble CD25 
      efficiently inhibited the proliferation of activated T cells and that blockade of 
      CD25 function abolished the induction of regulatory T cells by IL-10DCs, 
      indicating a critical role for IL-10DC-related CD25 in shifting the immune 
      response toward an iTreg(-) controlled tolerance reaction. In conclusion, the 
      selective use of the CD83(high) IL-10DC subset may result in a higher efficacy of 
      tolerance induction in vivo and may support the development of novel DC 
      vaccination strategies for transplantations, as well as for allergic and 
      autoimmune diseases.
CI  - Copyright (c) 2016 by The American Association of Immunologists, Inc.
FAU - Kryczanowsky, Fanny
AU  - Kryczanowsky F
AD  - Department of Dermatology, University Medical Center, Johannes 
      Gutenberg-University of Mainz, 55131 Mainz, Germany; and.
AD  - Institute of Immunotherapy, University Medical Center, Johannes 
      Gutenberg-University of Mainz, 55131 Mainz, Germany.
FAU - Raker, Verena
AU  - Raker V
AD  - Department of Dermatology, University Medical Center, Johannes 
      Gutenberg-University of Mainz, 55131 Mainz, Germany; and.
AD  - Institute of Immunotherapy, University Medical Center, Johannes 
      Gutenberg-University of Mainz, 55131 Mainz, Germany.
FAU - Graulich, Edith
AU  - Graulich E
AD  - Department of Dermatology, University Medical Center, Johannes 
      Gutenberg-University of Mainz, 55131 Mainz, Germany; and.
AD  - Institute of Immunotherapy, University Medical Center, Johannes 
      Gutenberg-University of Mainz, 55131 Mainz, Germany.
FAU - Domogalla, Matthias P
AU  - Domogalla MP
AD  - Department of Dermatology, University Medical Center, Johannes 
      Gutenberg-University of Mainz, 55131 Mainz, Germany; and.
AD  - Institute of Immunotherapy, University Medical Center, Johannes 
      Gutenberg-University of Mainz, 55131 Mainz, Germany.
FAU - Steinbrink, Kerstin
AU  - Steinbrink K
AD  - Department of Dermatology, University Medical Center, Johannes 
      Gutenberg-University of Mainz, 55131 Mainz, Germany; and 
      kerstin.steinbrink@unimedizin-mainz.de.
AD  - Institute of Immunotherapy, University Medical Center, Johannes 
      Gutenberg-University of Mainz, 55131 Mainz, Germany 
      kerstin.steinbrink@unimedizin-mainz.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160928
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, CD)
RN  - 0 (CCR7 protein, human)
RN  - 0 (Chemokine CCL21)
RN  - 0 (IL10 protein, human)
RN  - 0 (Immunoglobulins)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, CCR7)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Antigens, CD/metabolism
MH  - Cell Differentiation
MH  - Cell Movement
MH  - Cells, Cultured
MH  - Chemokine CCL21/metabolism
MH  - Dendritic Cells/*immunology/transplantation
MH  - Humans
MH  - Immune Tolerance
MH  - Immunoglobulins/metabolism
MH  - Immunotherapy/*methods
MH  - Inflammation/*immunology
MH  - Interleukin-10/*immunology
MH  - Interleukin-2 Receptor alpha Subunit/metabolism
MH  - Lymphocyte Activation
MH  - Membrane Glycoproteins/metabolism
MH  - Receptors, CCR7/metabolism
MH  - T-Lymphocytes, Regulatory/*immunology
MH  - CD83 Antigen
EDAT- 2016/09/30 06:00
MHDA- 2017/08/15 06:00
CRDT- 2016/09/30 06:00
PHST- 2015/08/04 00:00 [received]
PHST- 2016/09/01 00:00 [accepted]
PHST- 2016/09/30 06:00 [pubmed]
PHST- 2017/08/15 06:00 [medline]
PHST- 2016/09/30 06:00 [entrez]
AID - jimmunol.1501769 [pii]
AID - 10.4049/jimmunol.1501769 [doi]
PST - ppublish
SO  - J Immunol. 2016 Nov 1;197(9):3607-3617. doi: 10.4049/jimmunol.1501769. Epub 2016 
      Sep 28.