Multiple Sclerosis and Neuroimmunology

Experimental autoimmune encephalitis (EAE) is a multiple sclerosis (MS) animal model used to explore the pathogenesis of inflammation, demyelination and axonal loss. We showed that the hepatocyte growth factor (HGF), known for its strong neuroprotective properties and potentially remyelinating function, was able to inhibit the clinical course of EAE when specifically overexpressed in the central nervous system. We showed that this effect was mediated through immunomodulatory effects including the tolerization of dendritic cells and inhibition of T cell function at different levels including Treg. We also reported recently that interferon-beta, a medication used to treat MS, enhances HGF production in vivo by human monocytes. Further studies indicated that HGF: i) mediates in experimental MS its immunomodulatory effects via the GILZ signaling, ii) modulates the immunogenic functions of human antigen-presenting cells, and iii) decreases the cytotoxic activity of T lymphocytes. A recent project identified a novel population of highly cytotoxic c-Met-expressing CD8+ T lymphocytes that inhibits tumor growth. We are currently working on the role of CD4-cMet+ T cells in EAE and MS (SNF project). Collectively, our results suggest that the cMet-HGF pathway could play a key role in the attenuation of autoimmune disorders such as MS and could also modulate the immune response in cancer.

Specific expertise

• Fundamental and clinical neuroimmunology
• Multiple sclerosis and experimental autoimmune encephalomyelitis
• Immunoregulatory role of HGF and cMet receptor
• Role of biomarkers in autoimmune neurological diseases (serum and CSF).
• Mechanism of action of immunosuppressive drugs in multiple sclerosis.
• Risk of vaccination in multiple sclerosis

Selected publications

Huttner A, Eperon G, Lascano AM, Roth S, Schwob JM, Siegrist CA, Lalive PH. Risk of MS relapse after yellow fever vaccination: A self-controlled case series. Neurol Neuroimmunol Neuroinflamm. 2020 May 1;7(4):e726

Baert L, Benkhoucha M, Popa N, Ahmed MC, Manfroi B, Boutonnat J, Sturm N, Tessier M, Casez O, Marignier R, Ahmadi M, Broisat A, Ghezzi C, Rivat C, Sonrier C, Hahne M, Baeten D, Vives RR, Lortat H, Marche PN, Schneider P, Lassmann HP, Boucraut J, Lalive PH*, Huard B* (co-last author*).A proliferation-inducing ligand-mediated anti-inflammatory response of astrocytes in multiple sclerosis. Ann Neurol. 2019 Mar;85(3):406-420

Benkhoucha M, Molnarfi N, Kaya G, Belnoue E, Bjarnadóttir K, Dietrich PY, Walker PR, Martinvalet D, Derouazi M, Lalive PH. Identification of a novel population of highly cytotoxic c-Met-expressing CD8+ T lymphocytes. EMBO Rep. 2017 Sep;18(9):1545-1558

Molnarfi N, Benkhoucha M, Funakoshi H, Nakamura T, Lalive PH. Hepatocyte growth factor: A regulator of inflammation and autoimmunity. Autoimmun Rev. 2015 Apr;14(4):293-303

Benkhoucha M, Molnarfi N, Dunand-Sauthier I, Merkler D, Schneiter G, Bruscoli S, Riccardi C, Tabata Y, Funakoshi H, Nakamura T, Reith W, Santiago-Raber ML, Lalive PH. Hepatocyte growth factor limits autoimmune neuroinflammation via glucocorticoid-induced leucine zipper expression in dendritic cells. J Immunol. 2014 Sep 15;193(6):2743-52

Multiple Sclerosis