Toll-like receptor 3 differently modulates inflammation in progressive or benign multiple sclerosis

作者：Saresella Marina; Gatti Andrea; Tortorella Paola; Marventano Lvana; Piancone Federica; La Rosa Francesca; Caputo Domenico; Rovaris Marco; Biasin Mara; Clerici Mario^*

来源：Clinical Immunology, 2014, 150(1): 109-120.

DOI：10.1016/j.clim.2013.10.012

• Toll like receptors
• TLR3
• Neuroinflammation
• Multiple sclerosis
• Signal transduttion

TLR-dependent signal transduction pathways were analyzed in patients with a diagnosis of either relapsing remitting (RRMS), secondary progressive (PMS) or benign (BMS) MS and healthy controls (NC). Prototypical TLR molecules expressed either on the cell surface (TLR4) or intracellularly (TLR3) were stimulated with specific antigens (LPS and poly I:C, respectively). Expression of factors involved in TLR signaling cascades, production of downstream immune mediators and TLR expression were evaluated. Results showed that, whereas LPS-stimulation of TLR4 had a marginal effect on cell activation, poly I:C-stimulated TLR3 expression on immune cells was significantly increased in PMS and BMS compared to NC. This was associated with a higher responsiveness to poly I:C that resulted in the activation of the TLR3-mediated pathway and the production of inflammatory cytokines in PMS and, in contrast, in the up-regulation of a peculiar mosaic of inflammation-dampening genes in BMS. Results herein might explain different MS disease phenotypes.

• 出版日期2014-1