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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Vladislav Volarevic
  • Bojana Simovic Markovic
  • Sanja Bojic
  • Maja Stojanovic
  • Ulf Nilsson
  • Hakon Leffler
  • Gurdyal S. Besra
  • Nebojsa Arsenijevic
  • Verica Paunovic
  • Vladimir Trajkovic
  • Miodrag L. Lukic
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area

Keywords

  • Dendritic cells, Gal-3, Hepatitis, NKT cells, Regulatory T (Treg) cells
Original languageEnglish
Pages (from-to)531-543
JournalEuropean Journal of Immunology
Volume45
Issue number2
Publication statusPublished - 2015
Publication categoryResearch
Peer-reviewedYes