The Tolllike Receptor 2 (TLR2)related Immunopathological Responses in the Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Tolllike receptors (TLRs) play principle roles in recognition of autologous components which have been pointed as the dangerassociated molecular patterns (DAMP) and microbial components which are identified as pathogen associated molecular patterns (PAMP).The infiltration of various inflammatory cells such as dendritic cells, lymphocytes (CD4+ T, CD8+ #xA0;T as well as B cells), monocytes and macrophages occur into the central nervous sys #xAD;tem (CNS) during multiple sclerosis (MS) and its animal model named experimental autoimmune encephalomyelitis (EAE). The infiltrated leukocytes and residential cells of the CNS express several TLRs (especially TLR2) and their expression are elevated in MS and EAE. TLR2 recognizes a large variety DAMP and PAMP molecules due to its ability to create heterodimers with TLR1, TLR6 and probably TLR10. A wide spectrum of #xA0; DAMP molecules, including heat shock protein 60 (HSP60), HSP70, high mobility group box 1 (HMGB1), #x3B2;defensin 3, surfactant protein A and D, eosinophilderived neurotoxin, gangliosides, serum amyloid A, hyaluronic acid and biglycan are identified by TLR2, whose their expression is increased in MS patients. TLR2 may contribute in the development of MS and EAE diseases through the reinforcement of Th1/Th17 cellrelated responses, downregulation of regulatory T cells, induction of IL17+ #x3B3; #x3B4; T cells, inhibition of oligodendrocyte maturation, induction of poly ADPribose polymerase1 (PARP1)dependent pathway in microglia, macrophages and astrocytes and inhibition of type I interferons expression. The contribution of TLR2related immunopathological responses in the MS and EAE pathogenesis and its possible targeting as promising therapeutic potentials are considered in this review. #xA0;