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. 2013 Feb 27;2(1):75-93.
Print 2013.

Role of toll-like receptors in multiple sclerosis

Socorro Miranda-Hernandez  1 , Alan G Baxter
Affiliations

Role of toll-like receptors in multiple sclerosis

Socorro Miranda-Hernandez et al. Am J Clin Exp Immunol. .

Abstract

Multiple Sclerosis (MS) is an autoimmune disease in which Central Nervous System (CNS) lesions result from perivascular immune cell infiltration associated with damage to myelin, oligodendrocytes and neurons. CNS autoimmunity and its regulation are dominated by the inflammatory cytokines IL17 and IFNγ, and the opposing regulatory cytokines IL10 and the type I IFNs. Toll-like receptors (TLR) play a critical role in modulating cytokine and chemokine secretion in response to exogenous Pathogen Associated to Molecular Patterns and endogenous Danger-Associated to Molecular Patterns. Here, we systematically examine the evidence that TLR play a major role in the initiation disease, the triggering of relapses, and regulation of CNS damage. Data from human studies are supported analyses of a variety of animal models, including Experimental Autoimmune Encephalomyelitis in TLR-deficient mice.

Keywords: Multiple sclerosis; TLR1; TLR10; TLR2; TLR3; TLR4; TLR5; TLR6; TLR7; TLR8; TLR9; autoimmunity; gene/environment interactions; hygiene hypothesis; microbial flora; toll-like receptors.

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Figures

Figure 1
Figure 1
Toll-like receptors in Multiple Sclerosis. Ligation of TLR2 and TLR4 induces the production of IL1, IL6 and IL12, which induce the differentiation of naïve T cells into Th1 and Th17 cells. Th17 and Th1 cells secrete IL17 and INFγ respectively. IL17/INFγ-producing cells facilitate leukocyte migration across the blood-brain barrier and contribute to CNS damage. IL1 and IL6 also inhibit the differentiation of induced regulatory T cells (iTregs). Tregs are a major source of IL10, a cytokine that plays a critical role in suppressing CNS autoimmunity. Activation of TLR3, TLR7 and/or TLR9 can lead to the production of IFNβ, which activates T suppressor cells and inhibits the production of IL17 and IL23.
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