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Gal-3 regulates the capacity of dendritic cells to promote NKT-cell-induced liver injury

Volarevic, Vladislav; Markovic, Bojana Simovic; Bojic, Sanja; Stojanovic, Maja; Nilsson, Ulf LU ; Leffler, Hakon LU ; Besra, Gurdyal S.; Arsenijevic, Nebojsa; Paunovic, Verica and Trajkovic, Vladimir, et al. (2015) In European Journal of Immunology 45(2). p.531-543
Abstract
Galectin-3 (Gal-3), an endogenous lectin, exhibits ro- and anti-inflammatory effects in various disease conditions. In order to explore the role of Gal-3 in KT-cell-dependent pathology, we induced hepatitis in C57BL/6WT and al-3-deficient mice by using specific ligand for KT cells: alpha-galactosylceramide, glycolipid Ag presented by CD1d. The injection of alpha-galactosylceramide significantly enhanced expression of Gal-3 in liver NKT and dendritic cells (DCs). Genetic deletion or selective inhibition of Gal-3 (induced by Gal-3-inhibitor TD139) abrogated the susceptibility to NKT-cell-dependent hepatitis. Blood levels of pro-inflammatory cytokines (TNF-alpha-, IFN-gamma, IL-12) and their production by liver DCs and NKT cells were also... (More)
Galectin-3 (Gal-3), an endogenous lectin, exhibits ro- and anti-inflammatory effects in various disease conditions. In order to explore the role of Gal-3 in KT-cell-dependent pathology, we induced hepatitis in C57BL/6WT and al-3-deficient mice by using specific ligand for KT cells: alpha-galactosylceramide, glycolipid Ag presented by CD1d. The injection of alpha-galactosylceramide significantly enhanced expression of Gal-3 in liver NKT and dendritic cells (DCs). Genetic deletion or selective inhibition of Gal-3 (induced by Gal-3-inhibitor TD139) abrogated the susceptibility to NKT-cell-dependent hepatitis. Blood levels of pro-inflammatory cytokines (TNF-alpha-, IFN-gamma, IL-12) and their production by liver DCs and NKT cells were also downregulated. Genetic deletion or selective inhibition of Gal-3 alleviated influx of inflammatory CD11c(+) CD11b(+) DCs in the liver and favored tolerogenic phenotype and IL-10 production of liver NKT and DCs. Deletion of Gal-3 attenuated the capacity of DCs to support liver damage in the passive transfer experiments and to produce pro-inflammatory cytokines in vitro. Gal-3-deficient DCs failed to optimally stimulate production of pro-inflammatory cytokines in NKT cells, in vitro and in vivo. In conclusion, Gal-3 regulates the capacity of DCs to support NKT-cell-mediated liver injury, playing an important pro-inflammatory role in acute liver injury. (Less)
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publication status
published
subject
keywords
Dendritic cells, Gal-3, Hepatitis, NKT cells, Regulatory T (Treg) cells
in
European Journal of Immunology
volume
45
issue
2
pages
531 - 543
publisher
John Wiley & Sons
external identifiers
  • wos:000349625400022
  • scopus:84923040035
ISSN
1521-4141
DOI
10.1002/eji.201444849
language
English
LU publication?
yes
id
f5068278-3b81-4368-b4e4-1775e9e20eff (old id 5160213)
date added to LUP
2015-04-01 07:39:47
date last changed
2017-10-01 03:30:36
@article{f5068278-3b81-4368-b4e4-1775e9e20eff,
  abstract     = {Galectin-3 (Gal-3), an endogenous lectin, exhibits ro- and anti-inflammatory effects in various disease conditions. In order to explore the role of Gal-3 in KT-cell-dependent pathology, we induced hepatitis in C57BL/6WT and al-3-deficient mice by using specific ligand for KT cells: alpha-galactosylceramide, glycolipid Ag presented by CD1d. The injection of alpha-galactosylceramide significantly enhanced expression of Gal-3 in liver NKT and dendritic cells (DCs). Genetic deletion or selective inhibition of Gal-3 (induced by Gal-3-inhibitor TD139) abrogated the susceptibility to NKT-cell-dependent hepatitis. Blood levels of pro-inflammatory cytokines (TNF-alpha-, IFN-gamma, IL-12) and their production by liver DCs and NKT cells were also downregulated. Genetic deletion or selective inhibition of Gal-3 alleviated influx of inflammatory CD11c(+) CD11b(+) DCs in the liver and favored tolerogenic phenotype and IL-10 production of liver NKT and DCs. Deletion of Gal-3 attenuated the capacity of DCs to support liver damage in the passive transfer experiments and to produce pro-inflammatory cytokines in vitro. Gal-3-deficient DCs failed to optimally stimulate production of pro-inflammatory cytokines in NKT cells, in vitro and in vivo. In conclusion, Gal-3 regulates the capacity of DCs to support NKT-cell-mediated liver injury, playing an important pro-inflammatory role in acute liver injury.},
  author       = {Volarevic, Vladislav and Markovic, Bojana Simovic and Bojic, Sanja and Stojanovic, Maja and Nilsson, Ulf and Leffler, Hakon and Besra, Gurdyal S. and Arsenijevic, Nebojsa and Paunovic, Verica and Trajkovic, Vladimir and Lukic, Miodrag L.},
  issn         = {1521-4141},
  keyword      = {Dendritic cells,Gal-3,Hepatitis,NKT cells,Regulatory T (Treg) cells},
  language     = {eng},
  number       = {2},
  pages        = {531--543},
  publisher    = {John Wiley & Sons},
  series       = {European Journal of Immunology},
  title        = {Gal-3 regulates the capacity of dendritic cells to promote NKT-cell-induced liver injury},
  url          = {http://dx.doi.org/10.1002/eji.201444849},
  volume       = {45},
  year         = {2015},
}