Acta Medica Medianae (Dec 2010)
ROLE OF TH1 AND TH17 IMMUNE RESPONCES IN PATHOGENESIS OF MULTIPLE SCLEROSIS
Abstract
Th17 cells are novel cell subpopulation of CD4 + T lymphocytes which dominantly produce proinflammatory cytokine IL-17. Since their discovery in 2003, Th17 cells have been in the focus of interest, because of the numerous data pointing out their crucial significance in pathogenesis of multiple sclerosis and other disorders earlier considered as classical Th1-mediated autoimmune disorders. It is demonstrated, on animal model of multiple sclerosis, also known as experimental autoimmune encephalomyelitis, that Th17 cells are the main mediators of inflammatory process in autoimmunity, since Th1 cells have protective role, which is in contrast to the current concept of multiple sclerosis. Th17 and Th1 cell relationship determine if inflammation initiation and forming of demyelinisation plaque will occur. Inflammation will take place, if relationship between Th17 and Th1 cells is higher than 1 because of disproportional enhanced secretion of IL-17, which is considered to be the main regulator of autoimmune processes in the central nervous system. Discovery of TGF-β and IL-6 involvement in proinflammatory Th17 cells development was also surprising, according to the fact that TGF-β, itself, has anti-inflammatory effects and induces the activation of FOXP3 transcription factor, essential for the generation of regulatory T lymphocytes, the cells important for immunosuppression, development and maintenance of immunotolerance. Functional antagonism and similar differentiation factors of Th17 cells and regulatory T cells are very interesting in the aspect of immunomodulation therapy of autoimmune disorders. The aforementioned discoveries have constructed a novel concept of pathogenic mechanisms involved in multiple sclerosis development, mediated mainly by Th17 cells. That questions our knowledge of drug effect mechanisms that we commonly use today, but also raises the possibility for novel therapeutic approaches.
