Immunobiology of neurological disorders
The main focus of Immunobiology of neurological disorders Unit is the study of the biological processes associated with multiple sclerosis. Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) characterized by the loss of the myelin sheath surrounding the axons leading to alterations of the action potential propagation. It is presumably an autoimmune disease, as MS lesions present immune cell infiltration and the animal model of disease, the experimental autoimmune encephalomyelitis (EAE), is induced by immunization with myelin antigens. This leads to the activation of encephalitogenic T lymphocytes that enter the CNS, attack the myelin-forming cells (the oligodendrocytes) and start an inflammatory reaction that is amplified by CNS resident cells as the astrocytes and the microglia and by infiltrating immune cells. The currently used therapeutics for MS patients are immunosuppressive and immunomodulatory drugs, indicating that peripheral processes sustain disease. Thus, both central and peripheral events are involved in MS and need to be investigated.
The scientific activity of the Unit has been and is currently driven by a translational approach. Taking the moves from clinical observations and from human samples (blood or cerebral tissue), group research explores the activity of immune/glial/neuronal cells in vitro, sums up the high-throughput generated data with systems biology approaches, goes to the in vivo mouse models, until it is ready to go back to the clinic via the identification of novel diagnostic and prognostic biomarkers and the proposition of new therapeutic targets and approaches.
CNS Homeostasis and Pathology
• Reactive glia in neurodegenerative disorders
• Neuroprotective vs neuroinflammatory role of astrocytes
• Interaction between glia and neuronal or immune cells
• Neuroprotective properties of current MS therapeutics
Transcriptomics, bioinformatics and systems biology in neurological disorders
• Functional Genomics in Clinically Isolated Syndromes and MS
• Genetic and transcriptional protein networks in neurological disorders
• Functional annotation, target identification and validation
Monitoring immunomodulatory therapies for multiple sclerosis
• Pharmaco-transcriptomics and biomarker identification
• Immunological tests for MS therapeutics
Basic Neuroimmunology: Interaction between nervous and immune system
• Activation of immune cells by neurotrophic factors
• Neurotrophins and T cell development and activation
Srinivasan S, Severa M, Rizzo F, Menon R, Brini E, Mechelli R, Martinelli V, Hertzog P, Salvetti M, Furlan R, Martino G, Comi G, Coccia E, Farina C.
Transcriptional dysregulation of Interferome in experimental and human Multiple Sclerosis. Scientific Reports 7:8981, 2017.
Srinivasan S, Di Dario M, Russo A, Menon R, Brini E, Romeo M, Sangalli F, Dalla Costa G, Rodegher M, Radaelli M, Moiola L, Cantarella D, Medico E, Martino G, Furlan R, Martinelli V, Comi G, Farina C. Dysregulation of multiple sclerosis risk genes and pathways at distinct stages of disease. Neurol Neuroimmunol Neuroinflamm 2017 Mar 16;4(3):e337.
Colombo E, Farina C. Astrocytes: key regulators in neuroinflammation. Trends in Immunology 2016 Sep;37(9):608-620.
Di Dario M, Colombo E, Govi C, De Feo D, Messina MJ, Romeo M, Sangalli F, Moiola L, Rodegher M, Martino G, Martinelli V, Comi G, Farina C. Myeloid cells as target of fingolimod action in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 2015 Nov 4;2(6):e157.
Colombo E, Di Dario M, Capitolo E, Chaabane L, Newcombe J, Martino G, Farina C. Fingolimod may support neuroprotection via blockade of astrocyte nitric oxide. Annals Neurol. 2014 Sep;76(3):325-37.
Colombo E, Bedogni F, Lorenzetti I, Landsberger N, Previtali SC, Farina C. Autocrine and immune cell derived BDNF in human skeletal muscle: implications for myogenesis and tissue regeneration. J. Pathology. 2013 Oct;231(2):190-8.
Menon R, Di Dario M, Cordiglieri C, Musio S, La Mantia L, Milanese C, Di Stefano AL, Crabbio M, Franciotta D, Bergamasch Ri, Pedotti R, Medico E, Farina C. Gender-based blood transcriptomes and interactomes in multiple sclerosis: Involvement of SP1 dependent gene transcription. J. Autoimmunity. 2012 May;38(2-3):J144-55.
Colombo E, Cordiglieri C, Melli G, Newcombe J, Krumbholz M, Parada L, Medico E, Hohlfeld R, Meinl E, Farina C. Stimulation of the neurotrophin receptor TrkB on astrocytes drives nitric oxide production and neurodegeneration. J.Exp. Med. 2012 Mar 12;209(3):521-35.
Farina C, Aloisi F, Meinl E. Astrocytes are active players in cerebral innate immunity. Review. Trends in Immunology 2007 Mar;28(3):138-45.
Farina C, Weber MS, Meinl E, Wekerle H, Hohlfeld R. Glatiramer Acetate (GLAT) in multiple sclerosis: Update on potential mechanisms of action. Review. Lancet Neurology 2005 Sep;4(9):567-75.