Université de Genève

Neuroscience center

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Group leader: Patrice Lalive

Group name: Neuroimmunology

Affiliation: Medical Sciences & University Hospital

Research activities:

image Our group is interested in both fundamental and clinically-oriented research projects in inflammatory/demyelinating diseases of the central nervous system (CNS), and in particular on the pathogenesis and regulation of Multiple Sclerosis (MS). Our major interests are (i) the search for new biomarkers for MS inflammation and neurodegeneration, such as anti-myelin antibodies, interleukins and neurofilaments, and (ii) the identification of the mechanisms of action of current MS therapies, such as interferon (IFN)-beta, glatiramer acetate (GA) and natalizumab. In this context, we recently demonstrated that IFN-beta, a disease-modifying drug with strong anti-inflammatory properties, modulates the production of brain-derived neurotrophic factor, indicating that IFN-beta may also contribute directly to neuroprotection in MS patients (J Neuroimmunol, 2008). Other studies from our group indicate that GA inhibits pathogenic human T cell differentiation (J Neuroimmunol, 2007) and affects human monocytes by triggering a bias toward a less inflammatory profile (Proc Natl Acad Sci U S A, 2009).
Because of its many similarities to MS, experimental autoimmune encephalitis (EAE), the animal model of MS, is regularly used in our laboratory to study MS pathogenesis and regulation. As a main scientific breakthrough, we found that hepatocyte growth factor (HGF), a paracrine cellular growth, motility and morphogenic factor, inhibits CNS autoimmunity by inducing tolerogenic dendritic cells and regulatory T cells (Proc Natl Acad Sci U S A, 2010). As our data also indicate a role for HGF in neuroprotection (Eur J Immunol, 2005), we are currently developing new animal models to study the neuroprotective effects of HGF separate from its immune-regulating properties.
We have developed during the last five years collaborative studies with national and international laboratories of neuroimmunology in Zurich (USZ), Lausanne (CHUV) and San Francisco (UCSF).
The major research topics of our group are:

  • Multiple Sclerosis (MS) and demyelinating diseases of the CNS
  • Experimental Autoimmune Encephalitis (EAE)
  • Biomarkers of the serum and the cerebrospinal fluid in MS
  • Study of neuroprotective factors in EAE and MS
  • Study of Human Herpes-6 variant A and B in sporadic encephalitis
  • Selected Publications:

    • Benkhoucha M, Santiago-Raber ML, Schneiter G, Chofflon M, Funakoshi H, Nakamura T, Lalive PH.(2010)Hepatocyte growth factor inhibits CNS autoimmunity by inducing tolerogenic DCs and CD25+Foxp3+ regulatory T cells. Proceedings of the National Academy of Sciences of the United States of America, vol. 107(14) pp. 6424-6429
    • Burger D, Molnarfi N, Weber MS, Brandt KJ, Benkhoucha M, Gruaz L, Chofflon M, Zamvil SS, Lalive PH (2009)Glatiramer acetate increases IL-1 receptor antagonist but decreases T cell-induced IL-1beta in human monocytes and multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America, vol. 106(11) pp. 4355-4359
    • Lalive PH, Menge T, Delarasse C, Della Gaspera B, Pham-Dinh D, Villoslada P, von Büdingen HC, Genain CP.(2006)Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America, 2006 vol. 103(7) pp. 2280-2285
    • Other publications

    Contact:
    University Medical Center
    Département de Pathologie et Immunologie
    or
    Geneva University Hospital
    Département des Neurosciences Cliniques
    Service de Neurologie, Neuroimmunologie
    Email: Patrice (dot) Lalive (at) hcuge (dot) ch