Gal-3 regulates the capacity of dendritic cells to promote NKT-cell-induced liver injury
Författare
Summary, in English
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.
Avdelning/ar
Publiceringsår
2015
Språk
Engelska
Sidor
531-543
Publikation/Tidskrift/Serie
European Journal of Immunology
Volym
45
Issue
2
Dokumenttyp
Artikel i tidskrift
Förlag
John Wiley & Sons Inc.
Ämne
- Immunology in the medical area
Nyckelord
- Dendritic cells
- Gal-3
- Hepatitis
- NKT cells
- Regulatory T (Treg) cells
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1521-4141