title: Delineating the Role of Toll-Like Receptors in the Neuro-inflammation Model EAE.
abstract: Experimental autoimmune encephalomyelitis (EAE) is the most relevant and commonly used animal model to study autoimmune demyelinating diseases like Multiple Sclerosis (MS). In EAE, the activation of CD4+ T-cells is considered to be the main trigger leading to inflammation and central nervous system (CNS) demyelination. Toll-like receptors (TLRs) are the most important and first class of pattern recognition receptors (PRRs) in innate immune system and play critical roles in initiating inflammatory responses and promoting adaptive immune responses due to their ability to recognize a wide range of pathogen associated molecular patterns (PAMPs) and being expressed in a wide range of cell types both in the innate and adaptive immune systems. Upon TLR stimulation by appropriate ligand, innate immune cells produce pro-inflammatory cytokines and can serve as antigen-presenting cells (APCs) to prime naïve T cells to recognize antigens. Thus, TLRs play an important role in linking the innate to the adaptive immune response. To date, large numbers of studies have been done to investigate the role of adaptive immunity in both EAE and MS but delineating the role of innate immunity in EAE received very little focus and appreciation taking into account that it might contribute to both the initiation and progression of the disease. Moreover, EAE is not only a model to study inflammatory demyelination in the CNS; it is in general a model to study cell-mediated organ-specific autoimmune conditions. Roles of different TLRs were studied in relation to EAE and MS. More recently, some studies demonstrated the immune adjuvant properties of certain TLR ligands including TLR2, TLR4, and TLR9 in EAE. This chapter outlines different methods employed in our labs to investigate the role of TLRs in EAE model.
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fallarino
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Gargaro
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Giada
authors.initials: G
authors.lastname: Mondanell
authors.affiliation: School of Medicine, Discipline of Physiology, Trinity Biomedical Sciences Institute, Trinity College, Dublin 2, Ireland.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Downer
authors.affiliation: Division of Clinical Neuroscience, Queen's Medical Centre, University of Nottingham School of Medicine, C Floor South Block, Nottingham, NG7 2UH, UK.
authors.forename: Md Jakir
authors.initials: MJ
authors.lastname: Hossain
authors.affiliation: Division of Clinical Neuroscience, Queen's Medical Centre, University of Nottingham School of Medicine, C Floor South Block, Nottingham, NG7 2UH, UK. bruno.gran@nottingham.ac.uk.
authors.forename: Bruno
authors.initials: B
authors.lastname: Gran
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000378:metabolism*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D009103:Multiple Sclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000941:Antigens; D051193:Toll-Like Receptors
keywords: Antigen-presenting cells; Autoimmune disease; B cells; Demyelination; Dendritic cells; EAE; Inflammation; Multiple sclerosis; T cell; Toll-like receptors