- 23 March 2017
2:30 pm - 3:30 pm
Thursday 23 March 2017, 2.30 pm
Auditorium, Level 3, Central building
Phenotypic, functional and metabolic alterations in lymphocytes from patients with Multiple Sclerosis
Professor Andrea Cossarizza
Professor of Pathology, University of Modena & Reggio Emilia, School of Medicine
Hosted by Grace Chojnowski, Flow Cytometry and Imaging Facility Manager
Multiple sclerosis (MS) is a chronic progressive inflammatory demyelinating disorder of the central nervous system, with 4 clinical phenotypes: clinically isolated syndrome, relapsing-remitting (RR), secondary progressive (SP) and primary progressive (PP). Several cells of innate and adaptive immunity participate to its pathogenesis, including innate-like T lymphocytes such as invariant natural killer T (iNKT) cells. In 165 MS patients and 55 healthy controls, we found that the frequency of iNKT cells was similar among controls and patients with different forms and treatments of MS, but a Th1/Th17 cytokine bias were observed in MS patients. This was most prominent in SP patients, who displayed an increased production of IL-17 by CD4+ and CD8+ iNKT cells, suggesting a sustained iNKT cell activation and skewing towards a pro-inflammatory phenotype.
We then found that PP patients displayed a high percentage of terminally differentiated CD8+ T cells, along with low levels of CD8+ naïve T cells. Studying metabolism and mitochondrial functionality revealed that PP patients had a different modulation of transcription factors orchestrating metabolic switch, upregulation of glucose transporter-1 in CD4+ T cells, increased CD4+ and CD8+ effector memory T cells with phosphorylated ribosomal protein S6, indicating mTOR activation, smaller mitochondria, and decreased membrane potential.
Professor Cossarizza has many years of experience in Immunology, and in particular in the development and use of new flow cytometric approaches in immunological research. His longstanding research commitments are centered into identifying the molecular and cellular basis and the involvement of the immune system in several diseases and infections, such as HIV/AIDS or hepatitis, on the pathogenesis of sepsis, and physiopathological conditions, that include those of neurodegenerative origin (multiple sclerosis, Alzheimer) or human aging, either physiological (with the model of centenarians) and pathological (Down’s syndrome). During the past decade Professor Cossarizza has built expertise in the clinical application of new methods for the identification of rare cellular subsets to patients affected by HIV infection and to patients undergoing liver transplantation, as well as in patients suffering of multiple sclerosis or patients during septic shock. Such methods are allowing a new and fine characterization of the functional activities of these cells.