UNIGE document Scientific Article
previous document  unige:42844  next document
add to browser collection
Title

Hepatocyte growth factor limits autoimmune neuroinflammation via glucocorticoid-induced leucine zipper expression in dendritic cells

Authors
Bruscoli, Stefano
Riccardi, Carlo
Tabata, Yasuhiko
show hidden authors show all authors [1 - 13]
Published in Journal of Immunology. 2014, vol. 193, no. 6, p. 2743-52
Abstract Autoimmune neuroinflammation, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), a prototype for T cell-mediated autoimmunity, is believed to result from immune tolerance dysfunction leading to demyelination and substantial neurodegeneration. We previously showed that CNS-restricted expression of hepatocyte growth factor (HGF), a potent neuroprotective factor, reduced CNS inflammation and clinical deficits associated with EAE. In this study, we demonstrate that systemic HGF treatment ameliorates EAE through the development of tolerogenic dendritic cells (DCs) with high expression levels of glucocorticoid-induced leucine zipper (GILZ), a transcriptional repressor of gene expression and a key endogenous regulator of the inflammatory response. RNA interference-directed neutralization of GILZ expression by DCs suppressed the induction of tolerance caused by HGF. Finally, adoptive transfer of HGF-treated DCs from wild-type but not GILZ gene-deficient mice potently mediated functional recovery in recipient mice with established EAE through effective modulation of autoaggressive T cell responses. Altogether, these results show that by inducing GILZ in DCs, HGF reproduces the mechanism of immune regulation induced by potent immunomodulatory factors such as IL-10, TGF-β1, and glucocorticoids and therefore that HGF therapy may have potential in the treatment of autoimmune dysfunctions.
Identifiers
PMID: 25114100
Full text
Article (Author postprint) (1.5 MB) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research groups Métastases du foie (657)
Groupe Santiago-Raber Marie-Laure (pathologie et immunologie) (915)
Groupe Reith Walter (pathologie et immunologie) (282)
Scléroses en plaques, neuroimmunologie, encéphalite autoimmune expérimentale (843)
Citation
(ISO format)
BENKHOUCHA, Mahdia et al. Hepatocyte growth factor limits autoimmune neuroinflammation via glucocorticoid-induced leucine zipper expression in dendritic cells. In: Journal of Immunology, 2014, vol. 193, n° 6, p. 2743-52. https://archive-ouverte.unige.ch/unige:42844

198 hits

3 downloads

Update

Deposited on : 2014-12-09

Export document
Format :
Citation style :