Inflammatory Role of TLR-MyD88 Signaling in Multiple Sclerosis.

Chao Zheng,Jie Zhu,Tao Jin,Fengna Chu,Jingtao Chen

doi:10.3389/fnmol.2019.00314

Abstract

Multiple sclerosis (MS) is a neuro-autoimmune and neurodegenerative disorder leading to chronic inflammation, demyelination, axonal, and neuronal loss in the central nervous system (CNS). Despite intense research efforts, the pathogenesis of MS still remains unclear. Toll-like receptors (TLRs) are a family of type I transmembrane receptors that play a crucial role in the innate immune response. Myeloid differentiation factor 88 (MyD88) is the adaptor of major TLRs. It has been widely considered that the TLR-MyD88 signaling pathway plays an important role in the occurrence and development of autoimmune disease. Data have revealed that the TLR-MyD88 signaling may be involved in the pathogenesis of MS and experimental autoimmune encephalomyelitis (EAE), an animal model for MS, by regulating the antigen presentation of dendritic cells, the integrity of blood-brain barrier (BBB), and the activation of T cells and B cells. Here, we summarize the role of TLRs and MyD88 in MS and discuss the possible therapies that are based on these molecules.

Highlights

Multiple sclerosis (MS) is a neuro-autoimmune and neurodegenerative disorder leading to chronic inflammation, demyelination, axonal, and neuronal loss in the central nervous system (CNS)
Toll-like receptors (TLRs) are a family of type I transmembrane receptors that play a crucial role in the innate immune response (Li J. et al, 2013)
When stimulated by LPS, Dendritic cells (DCs) secreted high levels of IL-6 and IL-12, and the expressions of surface molecules increased slightly (Mirzaee et al, 2015). These results indicate that the activation of the TLR-Myeloid differentiation factor 88 (MyD88) signaling pathway can promote the evolution of DCs into a pathogenic status

Summary

INTRODUCTION

Multiple sclerosis (MS) is a neuro-autoimmune and neurodegenerative disorder leading to chronic inflammation, demyelination, axonal, and neuronal loss in the central nervous system (CNS). TLRs are a family of receptors involved in pathogen recognition and host defense They localize on the surface or in the endosomes of several immune-relevant cell types, such as macrophages, dendritic cells, T cells, B cells, astrocytes, oligodendrocytes, epithelial cells, and endothelial cells (Farrugia and Baron, 2017). TLRs are a family of type I transmembrane receptors that play a crucial role in the innate immune response (Li J. et al, 2013) They can recognize a wide variety of bacterial, fungal, protozoan, and viral components and can activate the immune response. MyD88 promotes the production of type I interferon by phosphorylating the transcription factor interferon-regulatory factor 7 (IRF7; Honda et al, 2004; Ning et al, 2011) These reports indicate that TLR-MyD88 signaling is an important trigger in inflammatory responses and that its abnormal functioning may cause autoimmune diseases or immunodeficiency

MS AND EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Pathogenic T Cells

Dendritic Cells

TLRs AND OTHER NEUROIMMUNE DISEASES

Findings

CONCLUSION