Projects per year
Galectin-3, an endogenous lectin, exhibits pro- and anti-inflammatory effects in various disease conditions. In order to explore the role of galectin-3 in NKT cell-dependent pathology, we induced hepatitis in C57BL/6 wild type and galectin-3 deficient mice by using specific ligand for NKT cells: α-galactosylceramide, glycolipid antigen presented by CD1d. The injection of α-galactosylceramide significantly enhanced expression of galectin-3 in liver NKT and dendritic cells (DCs). Genetic deletion or selective inhibition of galectin-3 (induced by galectin-3 inhibitor TD139) abrogated the susceptibility to NKT cell-dependent hepatitis. Blood levels of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-12) and their production by liver DCs and NKT cells were also down-regulated. Genetic deletion or selective inhibition of galectin-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 galectin-3 attenuated capacity of DCs to support liver damage in the passive transfer experiments and to produce pro-inflammatory cytokines in vitro. Galectin-3-deficient DCs failed to optimally stimulate production of pro-inflammatory cytokines in NKT cells, in vitro and in vivo. In conclusion, galectin-3 regulates the capacity of DCs to support NKT cell-mediated liver injury, playing an important pro-inflammatory role in acute liver injury. This article is protected by copyright. All rights reserved.
|Journal||European Journal of Immunology|
|Publication status||Published - 31 Oct 2014|
Bibliographical noteThis article is protected by copyright. All rights reserved.
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- 1 Finished
Design, synthesis, and assessment of specific iNKT cell agonists for clinical applications
Besra, D., Cox, L., Cunningham, A. & Lammas, T.
1/03/12 → 29/02/16
Project: Research Councils