Translational Autoimmunity, Volume 1: Etiology of Autoimmune Diseases

Description

Translational Autoimmunity: Etiology of Autoimmune Diseases is the first volume of the Translational Immunology book series. To attain its purpose as a detailed translational step to tackle autoimmunity, this volume sufficiently addresses basic questions on how the immune system is designed to distinguish self from nonself. It discusses the known mechanisms that lead to the maintenance of self-tolerance, presents potential triggers and malfunctions that impede normal immune processes, and demonstrates how the immune system induces an autoreactive state that results in the recognition of self-antigens seen in autoimmune conditions. Front Cover Translational Autoimmunity, Vol. 1: Etiology of Autoimmune Diseases Copyright Dedication Contents Contributors Preface Series editor biography Acknowledgment Abbreviations Chapter 1 Introduction on translational autoimmunity: From bench to bedside 1 Introduction 2 Autoimmune disorders 3 Pathogenesis and mechanisms of autoimmune diseases 4 Predisposing factors 5 Role of genetics 6 Obstacles in treatment 7 Diagnostic tools 8 Role of innate immunity 9 Conclusion References Chapter 2 Autophagy in autoimmunity 1 Introduction 2 An overview of autophagy 3 Autophagy in immunity 3.1 Autophagy in innate immunity 3.1.1 Elimination of pathogens by autophagy 3.1.2 Autophagy in inflammation regulation 3.2 Autophagy in adaptive immunity 3.2.1 Antigen presentation 3.2.2 Lymphocyte differentiation and survival Autophagy in T cells Autophagy in B cells 4 Autophagy in autoimmune diseases 4.1 Autophagy in SLE 4.2 Autophagy in RA 4.3 Autophagy in MS 4.4 Autophagy in AIH 5 Conclusion Acknowledgments Conflict of interest References Chapter 3 Immunometabolism and autoimmunity 1 Introduction 2 Immunometabolism in homeostasis 2.1 T cell metabolism 2.2 B cell metabolism 2.3 Macrophage metabolism 3 Immunometabolism in autoimmunity 3.1 SLE 3.2 RA 3.3 MS 3.4 Autoinflammatory diseases 4 Conclusion References Chapter 4 T cell recognition of neoepitopes in autoimmunity 1 Introduction 2 The mystery of lost tolerance in autoimmunity 3 Determinant spreading in autoimmune disease 4 Neoepitopes as a challenge to immune tolerance 4.1 Autoimmune susceptible HLA enhance presentation of neoepitope peptides 4.2 Increased TCR recognition of neoepitope peptides 5 T cell recognition of citrullinated neoepitopes in rheumatoid arthritis 6 T cell recognition of deamidated neoepitopes in CD 7 T cell recognition of neo-antigens in T1D 7.1 Cellular stress and upregulation of modifying enzymes 7.2 Cellular stress and alteration of the encoded proteome of target cells 8 Prospects for diagnostic detection of neoepitope specific T cell responses 9 Conclusion References Chapter 5 Role of Th1 and Th2 in autoimmunity 1 Introduction 1.1 Lymphocytes development, maturation, and “central tolerance” 1.2 Lymphocytes migration in the body and “peripheral tolerance” 1.3 Lymphocytes roles and plasticity: The Th1/Th2 hypothesis 2 Th1 and Th2 generation 2.1 Th1 polarization 2.2 Th2 polarization 3 Th1 and Th2 response in health 3.1 Th1 response 3.2 Th2 response 4 Breakdown of tolerance: Autoimmunity and allergy 4.1 Th1 in disease 4.2 Th2 in disease 5 Conclusion References Chapter 6 Role of Th17 cell in tissue inflammation and organ-specific autoimmunity 1 Introduction 2 Differentiation of IL-17-producing Th17 cells 3 Amplification of Th17 cells 4 Stabilization of Th17 cells 5 Transcriptional regulation of Th17 cells 6 Regulators of Th17 cells 6.1 IL-27 and Th17 cells 6.2 IL-10 and Th17 cells 6.3 IL-2 and Th17 cells 6.4 IL-25 and Th17 cells 6.5 STATS as a negative regulator of Th17 cells 7 Small molecules inhibitor of Th17 cells 8 Role of Th17 cells in the pathogenesis of autoimmune diseases 8.1 Alopecia areata 8.2 Systemic lupus erythematosus 8.3 Type 1 diabetes mellitus 8.4 Sjögren syndrome 8.5 Periodontitis and oral lichen planus 8.6 Autoimmune thyroid disorders 8.7 Noninfectious uveitis 8.8 Myasthenia gravis 8.9 Ankylosing spondylitis 8.10 Juvenile idiopathic arthritis 8.11 Systemic sclerosis 8.12 Psoriasis 8.13 Inflammatory bowel disease 8.14 Multiple sclerosis 8.15 Rheumatoid arthritis 9 Conclusion Acknowledgments References Chapter 7 Peptide editing and its modulation in CD4 + T cell tolerance to self 1 Introduction 2 Cellular adaptive immunity in health and disease 2.1 Basics of CD4 + T cell responses 2.2 HLA genes and proteins, and their link to autoimmunity 2.3 Basics of HLAII antigen presentation and the relevance of peptide editing 2.4 Peptide editing in different antigen presenting cells 2.5 Recognition of pMHCII by the TCR: The key step towards T cell activation 3 Tolerance mechanisms: training lymphocytes for a proper self and non-self recognition 3.1 Central tolerance 3.1.1 Positive selection 3.1.2 Negative selection or clonal deletion 3.1.3 Treg selection in the thymus 3.2 Peripheral tolerance 3.2.1 Ignorance 3.2.2 Anergy 3.2.3 Clonal deletion, peripheral Treg conversion and suppressor function 3.3 Peptide editing in the context of the affinity and avidity models for T cell activation and tolerance acquisition 4 Peptide editing in the targets of organ-specific autoimmune diseases 5 Conclusion References Chapter 8 Innate lymphoid cells in autoimmune diseases 1 Introduction 2 ILCs as crucial components of the mammalian immune system 2.1 Group 1 ILCs or ILC1s as potential innate immune lymphoid cells 2.2 Group 2 ILCs or ILC2s in immunity and inflammation 2.3 Group 3 ILCs or ILC3s in immunity and inflammation 3 ILCs in ADs 3.1 Group 1 ILCs or ILC1s in ADs 3.2 Group 2 ILCs or ILC2s in ADs 3.3 Group 3 ILCs or ILC3s in ADs 4 Conclusion References Chapter 9 Autoimmune diseases and the role of Toll-like receptor-7 and -9 signaling cascades 1 Introduction 2 Toll-like receptors 2.1 Introduction to TLRs 2.2 TLR7 and TLR9 expression patterns 2.3 Ligand-mediated activation of TLR7 and TLR9 downstream signaling 3 Autoimmune disorders with a role for TLR7 or TLR9 3.1 Systemic lupus erythematosus 3.2 Rheumatoid arthritis 3.3 Sjögren’s syndrome 3.4 Myositis 3.5 Multiple sclerosis 4 Manipulation of TLR7 and TLR9-induced signaling 4.1 TLR7 agonists 4.2 TLR7 antagonists 4.3 TLR9 agonists 4.4 TLR9 antagonists 4.5 Modifiers of TLR7 and TLR9 activation 5 Conclusion References Chapter 10 The role of type III interferons in systemic autoimmune diseases 1 Introduction 2 The type III interferon family 3 Production of type III interferons 4 Response of target cells to type III interferons 5 Potential association between interferons and autoimmunity 6 Type III interferons in systemic lupus erythematosus 7 Type III interferons in Sjögren syndrome 8 Type III interferons in rheumatoid arthritis 9 Type III interferons in antiphospholipid syndrome 10 Type III interferons in systemic sclerosis 11 Conclusion References Chapter 11 Regulation of immunological tolerance and human autoimmunity by NF- κ B 1 Introduction 1.1 Overview of NF- κ B proteins 1.2 Inhibition of NF- κ B 1.3 Pathways of NF- κ B activation 1.4 Regulation of NF- κ B 2 Immunological tolerance 2.1 Mechanisms of tolerance 2.2 Fundamental actions of NF- κ B and with implications for immunological tolerance 2.3 T cell tolerance 2.3.1 NF- κ B in thymic tolerance 2.3.2 NF- κ B and formation and maintenance of Tregs 2.4 B cell tolerance 2.4.1 Maintenance of peripheral self-tolerance in B cell compartment by BAFF 3 Monogenic NF- κ B defects and human autoimmunity 3.1 Defects in NF- κ B family 3.1.1 NFKB1 (p105/50) 3.1.2 NFKB2 (p100/52) 3.1.3 RELA 3.1.4 REL 3.2 Defects in NF- κ B activation 3.2.1 IKBKB 3.2.2 IKBKG (NEMO) 3.2.3 NIK 3.2.4 CHUK 3.3 Defects in inhibitors of NF- κ B 3.3.1 NFKBIA 3.4 Defects in upstream regulators of NF- κ B 3.4.1 CARD11, BCL10, and MALT1(CBM) complex 3.4.2 TNFRSF13C (BAFFR) 3.4.3 TNFAIP3 (A20) 3.4.4 OTULIN 4 Conclusion References Chapter 12 Micro RNA, circular RNA, neutrophils, and myeloperoxydases in autoimmune diseases 1 Introduction 2 Micro ribonucleic acids (MicroRNAs) 2.1 Rheumatoid arthritis (RA) 2.2 Systemic lupus erythematosus (SLE) 2.3 Primary Sjogren’s syndrome (PSS) 2.4 Multiple sclerosis (MS) 2.5 Psoriasis 2.6 Primary biliary cirrhosis (PBC) 2.7 Idiopathic thrombocytopenic purpura 2.8 Inflammatory bowel diseases (IBD) 3 Circular RNAs 3.1 Rheumatoid arthritis 3.2 Multiple sclerosis 3.3 Systemic lupus erythematosus 3.4 Primary biliary cirrhosis 3.5 Type 1 diabetes mellitus (T1DM) 4 Neutrophils 4.1 Neutrophils and their natural history 4.2 Neutrophils’ function 4.3 Neutrophils in systemic lupus erythematosus 4.4 Neutrophils in rheumatoid arthritis 4.5 ANCA-associated vasculitides (AAV) and neutrophils 4.6 Antiphospholipid syndrome and neutrophils 5 Myeloperoxidase in autoimmune diseases 6 Conclusion References Chapter 13 Human leukocyte antigen and autoimmunity 1 Introduction 2 HLA genetic organization and protein structure 3 Autoimmune HLA disease association 4 Mechanisms involved in HLA-mediated autoimmune pathology 4.1 Alternate docking 4.2 Altered register 4.3 Low-affinity-mediated thymic escape 4.4 T cell receptor stabilization of weak peptide–HLA complexes 4.5 “Hotspot” molecular mimicry 4.6 Post-translational modification 4.7 Hybrid peptides 4.8 Regulation of HLA expression 4.9 HLA molecular folding 4.10 HLA stability 5 Conclusion References Chapter 14 HLA-G-mediated immunological tolerance and autoimmunity 1 Introduction 2 Genetic variation of HLA-G gene 3 Molecular structure of HLA-G 3.1 HLA-G isoforms generated by the transcriptional process 3.2 HLA-G complex modified by the post-translational process 4 HLA-G expression regulation 5 HLA-G and receptor signaling pathways 5.1 HLA-G/ILTs signaling pathway 5.2 HLA-G/KIR2DL4 signaling pathway 5.3 HLA-G and other receptors signaling pathways 5.4 Intercellular transfer of HLA-G among immune cells 6 HLA-G and autoimmunity 6.1 HLA-G and systemic lupus erythematosus 6.2 HLA-G and rheumatoid arthritis 6.3 HLA-G and type I diabetes mellitus 6.4 HLA-G and multiple sclerosis 6.5 HLA-G and ankylosing spondylitis 6.6 HLA-G and systemic sclerosis 6.7 HLA-G and pemphigus 6.8 HLA-G and psoriasis 6.9 HLA-G and ulcerative colitis and Crohńs disease 7 Implication of HLA-G-mediated immune tolerance in autoimmunity 8 Conclusion Acknowledgments References Chapter 15 The immune system and the microbiota: The two sides of mucosal tolerance 1 Introduction 2 Microbiota 3 Mucosal immune system 4 Mucosal tolerance 5 Mechanisms of mucosal tolerance toward commensal bacteria 5.1 The barrier functions of the mucosal epithelia 5.1.1 The junctional complex 5.1.2 The mucus barrier 5.1.3 Cationic host defense peptides 5.1.4 Immune sensing of epithelial cells 5.2 The microbiota-to-mucosal immune system axis 5.2.1 Short-chain fatty acids (SCFAs) 5.2.2 Tryptophan metabolites 5.3 The mucosal immune system-to-microbiota axis 5.3.1 Unconventional T cells and antimicrobial peptides 5.3.2 IgA-producing B cells 6 Tolerance breaking at the mucous membranes and autoimmune diseases 7 Conclusion References Chapter 16 Role of free radicals in autoimmune diseases 1 Introduction 2 Pathophysiology of free radicals 3 Inflammation and autoimmune diseases 4 Rheumatoid arthritis 5 Systemic lupus erythematosus 6 Conclusion Acknowledgement Conflict of interest References Chapter 17 Immunological tolerance and autoimmunity 1 Introduction 2 Central tolerance of T cells and autoimmunity 2.1 Positive selection 2.2 Negative selection 3 Peripheral T cell tolerance and autoimmunity 3.1 Anergy 3.2 Peripheral deletion 3.3 Immunologically privileged sites 3.4 Regulatory/suppressor cells 4 Central B cell tolerance and autoimmunity 5 Peripheral B cell tolerance and autoimmunity 6 Conclusion References Chapter 18 Construction of bioscore for detection of self-tolerance failure: From analysis of silicosis cases 1 Introduction 2 Effects of silica particles on human immune cells 2.1 Autoantibodies found in SIL patients 2.2 Alteration of CD4    + responder T cells 2.3 Alteration of CD4    + Treg cells 2.4 Effects of silica particles on dendritic and Th17 cells 3 Generating a bioscore/autoimmune score to detect early dysregulation of autoimmunity 4 Conclusion Acknowledgments Conflicts of interest References Index Back Cover