Th17 cells in the pathogenesis of multiple sclerosis

Th17 cells are a recently described subset of T helper lymphocytes characterized by the production of IL-17 (IL-17A). Since their discovery in 2003, studies on Th17 cells have become increasingly popular among immunologists and they have emerged as key players in the pathogenesis of multiple sclerosis (MS) and other autoimmune disorders traditionally attributed to Th1 cells. Murine Th17 lymphocytes differentiate from naive CD4(+) cells in a specific cytokine environment, which includes TGF-beta and IL-6 or IL-21, whereas human Th17 cell development requires TGF-beta, IL-1 beta, and IL-2 in combination with IL-6, IL-21, or IL-23. Th17-related response is additionally enhanced by osteopontin, TNF alpha, and PGE2 and suppressed by IL-25, IL-27, IL-35, and IL-10. Apart from their main cytokine, Th17 cells can also express IL-17F, IL-21, IL-22, TNF alpha, CCL20, and, in humans, IL-26. All of these mediators may contribute to the proinflammatory action of Th17 cells both in the clearance of various pathogens and in autoimmunity. At least some of these functions are exerted through the induction of neutrophil-recruiting chemokines (CXCL1, CXCL2, CXCL8) by IL-17. Accumulating evidence from studies on mice and humans indicates an important role of Th17 cells in mediating autoimmune neuroinflammation. This has led some immunologists to question the previously exhibited importance of Th1 cells in MS pathology. However, more recent data suggest that both these T-cell subsets are capable of inducing and promoting the disease. Further investigation is required to clarify the role of Th17 cells in the pathogenesis of MS since some of the Th17-related molecules appear as attractive targets for future therapeutic strategies.