Scientific article
English

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

Published inThe Journal of immunology, vol. 193, no. 6, p. 2743-2752
Publication date2014
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.

Citation (ISO format)
BENKHOUCHA, Mahdia et al. Hepatocyte growth factor limits autoimmune neuroinflammation via glucocorticoid-induced leucine zipper expression in dendritic cells. In: The Journal of immunology, 2014, vol. 193, n° 6, p. 2743–2752. doi: 10.4049/jimmunol.1302338
Main files (1)
Article (Accepted version)
accessLevelRestricted
Identifiers
Journal ISSN0022-1767
671views
3downloads

Technical informations

Creation27/10/2014 14:04:00
First validation27/10/2014 14:04:00
Update time14/03/2023 22:23:05
Status update14/03/2023 22:23:05
Last indexation30/10/2024 21:12:21
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack