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

• Published in: Iranian journal of allergy, asthma, and immunology asthma, and immunology, 2019-06, Vol.18 (3), p.230
• Main Authors: Jafarzadeh, Abdollah, Nemati, Maryam, Khorramdelazad, Hossain, Mirshafiey, Abbas
• Format: Article
• Language: English
• Subjects: Amyloid; Animal models; Astrocytes; CD4 antigen; CD8 antigen; Central nervous system; Dendritic cells; Eosinophil-derived neurotoxin; Experimental allergic encephalomyelitis; Experimental autoimmune encephalomyelitis; Gangliosides; Heat shock proteins; Helper cells; High mobility group proteins; HMGB1 protein; Hsp60 protein; Hsp70 protein; Hyaluronic acid; Inflammation; Interferon; Interleukin 17; Lymphocytes B; Lymphocytes T; Microglia; Multiple sclerosis; Pathogenesis; Poly(ADP-ribose) polymerase; Toll like receptor 2; Toll-like receptors
• ISSN: 1735-1502; 1735-5249
• DOI: 10.18502/ijaai.v18i3.1117

Toll-like receptors (TLRs) play principle roles in recognition of autologous components which have been pointed as the danger-associated 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+ T as well as B cells), monocytes and macrophages occur into the central nervous sys­tem (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  DAMP molecules, including heat shock protein 60 (HSP60), HSP70, high mobility group box 1 (HMGB1), β-defensin 3, surfactant protein A and D, eosinophil-derived 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 cell-related responses, downregulation of regulatory T cells, induction of IL-17+ γδ T cells, inhibition of oligodendrocyte maturation, induction of poly ADP-ribose polymerase-1 (PARP-1)-dependent pathway in microglia, macrophages and astrocytes and inhibition of type I interferons expression. The contribution of TLR2-related immunopathological responses in the MS and EAE pathogenesis and its possible targeting as promising therapeutic potentials are considered in this review.