A single non-synonymous polymorphism reveals a modulatory role of Toll like receptor 2 on experimental autoimmune encephalomyelitis

Purpose: Toll like receptor 2 (TLR2) may regulate the mechanisms responsible for the development of experimental autoimmune encephalomyelitis (EAE), the widely used animal model that reproduces many of the features of multiple sclerosis (MS). The comparison between TLR2 of SJL and B6 showed the presence of a single non-synonymous nucleotide polymorphism (SNP) with the B6 (82Met) allele dominant over that of SJL (82Ile) (1). We crossed SJL and B6 mice to obtain F1(SJLxB6 tlr2-) and F1(SJLxB6wt) to examine the impact of this SNP (Met82Ile) on the EAE progression, distribution of lesions in the central nervous system (CNS), and on the pro/anti-inflammatory balance of T cells. Methods: F1(SJLxB6 tlr2-) and F1(SJLxB6wt) mice were immunized to induce EAE that was monitored for 50 days (2). Brains and spinal cords were stained to assess the inflammatory lesions and demyelination. mRNA from draining lymph nodes and CNS infiltrating cells of F1 mice were analyze by Real Time PCR for levels of pro/anti-inflammatory cytokines and expression of transcription factors. Results: Although TLR2 82Met doesn’t influence the incidence of EAE, it is a dominant attenuator of its clinical course. At the same time, it reduces remission of symptoms, modifies the distribution of CNS lesions and reduces the production of cytokines leading to Th1/Th17 polarization as well as ag-driven increase of FoxP3. Discussion: A limited genetic variation of an innate receptor is sufficient to produce complex effects on the clinical features of EAE. Conclusion: Our results suggest that TLR2 may represent a key regulator implicated in the ability of environment to modulate MS. Bibliography: (1) Nicolò et al.. PLoSOne. 2013;8(2). (2) Tuohy et al. J.Immunol.1988 Mar 15;140(6).