PMID- 25661445
OWN - NLM
STAT- MEDLINE
DCOM- 20150918
LR  - 20220129
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 100
IP  - 4
DP  - 2015 Apr
TI  - HLA-G expression levels influence the tolerogenic activity of human DC-10.
PG  - 548-57
LID - 10.3324/haematol.2014.113803 [doi]
AB  - Human leukocyte antigen (HLA)-G is a non-classical HLA class I molecule with 
      known immune-modulatory functions. Our group identified a subset of human 
      dendritic cells, named DC-10, that induce adaptive interleukin-10-producing T 
      regulatory type 1 (Tr1) cells via the interleukin-10-dependent HLA-G/ILT4 
      pathway. In this study we aimed at defining the role of HLA-G in DC-10-mediated 
      Tr1 cell differentiation. We analyzed phenotype, functions, and genetic 
      variations in the 3' untranslated region of the HLA-G locus of in 
      vitro-differentiated DC-10 from 67 healthy donors. We showed that HLA-G 
      expression on DC-10 is donor-dependent. Functional studies demonstrated that 
      DC-10, independently of HLA-G expression, secrete interleukin-10 and negligible 
      levels of interleukin-12. Interestingly, DC-10 with high HLA-G promote 
      allo-specific anergic T cells that contain a significantly higher frequency of 
      Tr1 cells, defined as interleukin-10-producing (P=0.0121) or CD49b(+)LAG-3(+) 
      (P=0.0031) T cells, compared to DC-10 with low HLA-G. We found that the HLA-G 
      expression on DC-10 is genetically imprinted, being associated with specific 
      variations in the 3' untranslated region of the gene, and it may be finely tuned 
      by microRNA-mediated post-transcriptional regulation. These data highlight the 
      important role of HLA-G in boosting DC-10 tolerogenic activity and confirm that 
      interleukin-10 production by DC-10 is necessary but not sufficient to promote Tr1 
      cells at high frequency. These new insights into the role of HLA-G in 
      DC-10-mediated induction of Tr1 cells provide additional information for clinical 
      use in Tr1- or DC-10-based cell therapy approaches.
CI  - Copyright(c) Ferrata Storti Foundation.
FAU - Amodio, Giada
AU  - Amodio G
AD  - San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of 
      Regenerative Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific 
      Institute, Milan, Italy Vita-Salute San Raffaele University, Milan, Italy.
FAU - Comi, Michela
AU  - Comi M
AD  - San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of 
      Regenerative Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific 
      Institute, Milan, Italy Ph.D Program in Translational and Molecular Medicine 
      (DIMET), University of Milan-Bicocca, Italy.
FAU - Tomasoni, Daniela
AU  - Tomasoni D
AD  - San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of 
      Regenerative Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific 
      Institute, Milan, Italy.
FAU - Gianolini, Monica Emma
AU  - Gianolini ME
AD  - San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of 
      Regenerative Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific 
      Institute, Milan, Italy Department of Public Health and Cell Biology, Tor Vergata 
      University, Rome, Italy.
FAU - Rizzo, Roberta
AU  - Rizzo R
AD  - Department of Medical Sciences, Section of Microbiology, University of Ferrara, 
      Italy.
FAU - LeMaoult, Joel
AU  - LeMaoult J
AD  - Service de Recherches en Hemato-Immunologie, CEA-DSV-DRM, Hopital Saint-Louis, 
      IUH, Paris, France.
FAU - Roncarolo, Maria-Grazia
AU  - Roncarolo MG
AD  - San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of 
      Regenerative Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific 
      Institute, Milan, Italy Vita-Salute San Raffaele University, Milan, Italy.
FAU - Gregori, Silvia
AU  - Gregori S
AD  - San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of 
      Regenerative Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific 
      Institute, Milan, Italy gregori.silvia@hsr.it.
LA  - eng
GR  - TGT11E02/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150206
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Cytokines)
RN  - 0 (HLA-G Antigens)
RN  - 0 (MIRN152 microRNA, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Alleles
MH  - Cell Differentiation
MH  - Clonal Anergy/genetics/immunology
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/cytology/*immunology/*metabolism
MH  - *Gene Expression
MH  - Gene Frequency
MH  - Genotype
MH  - HLA-G Antigens/*genetics/metabolism
MH  - Humans
MH  - Immune Tolerance/*genetics
MH  - Immunophenotyping
MH  - Membrane Glycoproteins/genetics/metabolism
MH  - MicroRNAs/genetics
MH  - T-Lymphocyte Subsets/cytology/immunology/metabolism
PMC - PMC4380729
EDAT- 2015/02/11 06:00
MHDA- 2015/09/19 06:00
PMCR- 2015/04/01
CRDT- 2015/02/10 06:00
PHST- 2015/02/10 06:00 [entrez]
PHST- 2015/02/11 06:00 [pubmed]
PHST- 2015/09/19 06:00 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - haematol.2014.113803 [pii]
AID - 1000548 [pii]
AID - 10.3324/haematol.2014.113803 [doi]
PST - ppublish
SO  - Haematologica. 2015 Apr;100(4):548-57. doi: 10.3324/haematol.2014.113803. Epub 
      2015 Feb 6.