Epigenetics in Allergy and Autoimmunity (Advances in Experimental Medicine and Biology Book 1253)

This book will address the growing roles of epigenetics in disease pathogenesis, and review the contribution of epigenetic modifications to disease onset and progression. The roles that epigenetics plays in facilitating effects of the environment on allergy and immunologic diseases will be reviewed. The book is divided into three parts – the first is an introduction to epigenetics and the methods that have been developed to study epigenetics, the second addresses epigenetics in allergic diseases and the third part will cover epigenetics in autoimmune diseases. With the rapid expansion of knowledge of how genes are regulated and how this regulation affects disease phenotypes, this book will be attractive to experienced researchers as well as those just launching an epigenetics research program. It will also be of interest to allergist, immunologists, rheumatologists and dermatologist who are engaged in clinical practice as a resource for understanding the basis for personalized and precision medicine. For example, the role that epigenetics plays in the pathogenesis in various allergic and autoimmune disorders and how this determines disease phenotypes will be covered extensively in this book. This book will thus help fill the gap in available resources on epigenetics in allergy and autoimmune diseases. Preface 7 Contents 9 Editors and Contributors 11 Part I Introduction 15 1 Epigenetics in Health and Disease 16 1.1 Introduction 17 1.2 The Science Behind Epigenetics 18 1.3 Epigenetics and Human Disease 19 1.4 The Clinical Application of Epigenetics 21 1.4.1 Epigenetic Biomarkers 21 1.4.2 Epigenetic Therapy 22 1.5 Epigenetic in Diseases 24 1.5.1 The Role of Epigenetics in Cancer 24 1.5.2 The Role of Epigenetics in Immune Diseases 29 1.5.3 Role of Epigenetics in Endocrine Diseases 34 1.5.4 The Role of Epigenetics in Respiratory System Diseases 38 1.5.5 The Role of Epigenetics in Dermatologic Disorders 43 1.5.6 Role of Epigenetics in Cardiovascular Diseases 48 1.5.7 The Role of Epigenetics in Gastrointestinal Tract Diseases 52 1.6 Discussion 57 1.7 Conclusion 57 References 58 2 The Development of Epigenetics in the Study of Disease Pathogenesis 69 2.1 The History and Discovery of the Basic Mechanics of Epigenetics 69 2.1.1 Experimental Observations: Setting the Stage for the Discovery of Epigenetic Mechanisms 69 2.1.2 Getting to the Substance of the Matter: Discoveries of Physical Mechanisms of Epigenetic Control 73 2.1.3 A New Epigenetic Role for RNA 76 2.2 Epigenetics Moves Mainstream and Meets the Clinic 77 2.2.1 The Epigenetics of Aging 78 2.2.2 The Concept of an Epigenetic Clock 88 2.2.3 Epigenetic Effects of Antiaging Interventions 92 2.3 Epigenetic Modifications as Biomarkers of Disease 93 2.4 Epigenetics in the Modern World: Using Big Data to Understand the Pathogenesis of Complex Diseases in the Present Day 96 2.5 Summary 100 References 101 3 Epigenetic Methods and Twin Studies 107 3.1 Introduction 108 3.2 Epigenetic Methods Applied to Rheumatic Diseases 108 3.3 Epigenetic Twin Studies in Rheumatic Diseases 110 3.4 Conclusions 113 References 114 Part II Allergic Diseases 117 4 The Role of Genetics, the Environment, and Epigenetics in Atopic Dermatitis 118 4.1 Introduction 118 4.2 Prevalence 119 4.3 Clinical Features 120 4.4 Diagnosis 120 4.5 Pathogenesis 121 4.5.1 Skin Barrier 121 4.5.2 Skin Barrier and AD 123 4.5.3 Immune Imbalance of AD 125 4.5.4 Interaction of Skin Barrier and Immune Function in AD 131 4.5.5 Environmental Factors 133 4.6 GWAS in AD 134 4.7 Epigenetics and AD 136 4.7.1 Epigenetic Studies on the Skin Barrier 137 4.7.2 Epigenetic Studies on the Immune System 139 4.7.3 miRNAs in AD 141 4.7.4 Epigenetics Studies in AD Patients 142 4.8 Conclusion 144 References 145 5 The Epigenetics of Food Allergy 152 5.1 Introduction 153 5.2 Biological Processes in Food Allergy 155 5.3 Genetics 156 5.3.1 Family History 156 5.3.2 Genes Involved in Food Allergy 157 5.4 The Environment 158 5.4.1 The Effect of Early Introduction of Foods 158 5.4.2 The Microbiome 158 5.5 Epigenetic Research in Food Allergies 159 5.6 Conclusions 161 References 161 6 Epigenetics and the Environment in Airway Disease: Asthma and Allergic Rhinitis 164 6.1 Introduction 165 6.2 Epigenetic Variation in the Course of Asthma and Allergic Rhinitis 168 6.2.1 The Role of Maternal Airway Disease 168 6.2.2 The Role of Demographic Variation 171 6.2.3 The Role of Biologic Variation 172 6.2.4 Disease-Associated Epigenetic Variation of Non-specific Origin 173 6.2.5 The Role of Environmental Exposure 175 6.2.6 The Role of Specific Genetic Haplotypes in Environmentally Induced Epigenetic Changes 182 6.3 Practical Application and Current Limitations 184 6.4 Conclusion 186 References 186 Part III Autoimmune Diseases 193 7 The Epigenetics of Lupus Erythematosus 194 7.1 Introduction 195 7.2 Epigenetic Regulation of the Pathogenesis of SLE 195 7.2.1 Epigenetic Regulation of Over-Activated Dendritic Cells (DCs) in SLE 195 7.2.2 Epigenetic Regulations of Dysregulated T Cells from SLE 198 7.2.3 Epigenetic Regulations on Autoreactive B Cells from SLE 201 7.2.4 Dysregulated Epigenetic Modifications in Signaling Pathways 202 7.2.5 Environmental Factor-Induced Epigenetic Alterations in SLE 204 7.3 Epigenetic Modifications as Biomarkers for SLE 204 7.3.1 DNA Methylation States Serve as Biomarkers in SLE 204 7.3.2 Non-coding RNAs Serve as Biomarkers in Lupus 207 7.4 Epigenetic Therapies in SLE 208 7.5 Conclusion 209 References 209 8 Epigenetics of Psoriasis 217 8.1 Introduction 217 8.2 DNA Methylation 218 8.2.1 Global Methylation 220 8.2.2 Candidate Gene Methylation 220 8.3 Histone Modifications 221 8.4 Noncoding RNA Regulation 222 8.4.1 MicroRNAs (MiRNAs)-Mediated Regulation 222 8.4.2 Long Noncoding RNA-Mediated Regulation 224 8.4.3 Circular RNA-Mediated Regulation 224 8.4.4 Treatment Targeting Epigenetic Regulation in Psoriasis 225 8.5 Conclusion 226 References 226 9 The Role of Epigenetics in Type 1 Diabetes 230 9.1 Introduction 231 9.2 Genetic Factors, Environmental Factors, and Epigenetics that Affect the Pathogenesis of T1D 232 9.2.1 Genetic Factors 233 9.2.2 Environmental Factors and Epigenetics 234 9.3 DNA Methylation and T1D 237 9.4 Histone Modifications and T1D 241 9.5 MicroRNAs and T1D 243 9.6 Clinical Applications of Epigenetics in T1D 247 9.6.1 Epigenetic Modifications as Biomarkers in T1D 247 9.6.2 Epigenetic Modifications in the Intervention of T1D 249 9.7 Conclusion 255 References 256 10 Epigenetics of Primary Biliary Cholangitis 265 10.1 Introduction 266 10.2 DNA Methylation 269 10.3 The Histone Modification 272 10.4 Noncoding RNAs 274 10.5 Telomere Dysregulation in BECs 280 10.6 Sex Chromosome Deficiency and PBC 281 10.7 Epigenetic Modification and Therapies 282 10.8 Conclusion 283 References 283 11 Epigenetics in Primary Sjögren’s Syndrome 290 11.1 Introduction 291 11.2 Environmental, Genetic, and Epigenetic Factors 292 11.2.1 Environmental Factors 292 11.2.2 Genetic Factors 293 11.2.3 Epigenetic Factors 293 11.3 Epigenetic Defects 295 11.3.1 DNA Methylation 295 11.3.2 Histones 299 11.3.3 miRNA 299 11.4 Epigenetic Reprogramming and Consequences 300 11.4.1 Methylation Modifications 300 11.4.2 Histone Modifications in SjS 304 11.4.3 miRNA in SjS 304 11.5 Genetic Risk Factors Associated with SjS and Related to Epigenetic Factors 305 11.5.1 Methylation Modification 305 11.5.2 Histone Modifications 305 11.5.3 miRNA Modification 307 11.6 Conclusions 307 References 307 12 Epigenetics in Multiple Sclerosis 314 12.1 Introduction 316 12.2 Clinical Staging and Immunopathogenesis of MS 316 12.3 Epigenetics of MS 318 12.3.1 DNA Methylation and MS 319 12.3.2 MicroRNAs and MS 330 12.3.3 Histone Modification and MS 350 12.4 Clinical Application Potential of Epigenetics Regulators in MS 356 12.4.1 Epigenetic Modifiers as Biomarkers in MS 356 12.4.2 Epigenetic Modifiers as Therapeutics for MS 361 12.5 Concluding Remarks 366 References 366 13 The Epigenetic Regulation of Scleroderma and Its Clinical Application 380 13.1 Introduction 382 13.2 Role of Epigenetics in the Pathogenesis of SSc 383 13.2.1 Epigenetics is Involved in Progressive Vasculopathy 384 13.2.2 Epigenetics is Involved in Immune Abnormalities 387 13.3 Epigenetics is Involved in Fibrosis 391 13.3.1 The Role of DNA Methylation in Fibrosis in SSc 391 13.3.2 Role of Histone Modification in Fibrosis in SSc 393 13.3.3 Role of microRNAs in Fibrosis in SSc 395 13.4 Epigenetic Biomarkers in SSc 398 13.4.1 DNA Methylation-Related Biomarkers in SSc 398 13.4.2 Histone Modification-Related Biomarkers in SSc 399 13.4.3 MicroRNAs-Related Biomarkers in SSc 399 13.5 Potential Therapeutic Effects of Epigenetics in SSc 400 13.5.1 Inhibition of DNA Methylation 400 13.5.2 Inhibitors of Histone Modification 401 13.5.3 MicroRNA Replacements 402 13.6 Conclusion 402 References 402 Front Matter ....Pages i-xiv Front Matter ....Pages 1-1 Epigenetics in Health and Disease (Lian Zhang, Qianjin Lu, Christopher Chang)....Pages 3-55 The Development of Epigenetics in the Study of Disease Pathogenesis (Matlock A. Jeffries)....Pages 57-94 Epigenetic Methods and Twin Studies (Angela Ceribelli, Carlo Selmi)....Pages 95-104 Front Matter ....Pages 105-105 The Role of Genetics, the Environment, and Epigenetics in Atopic Dermatitis (Zhanglei Mu, Jianzhong Zhang)....Pages 107-140 The Epigenetics of Food Allergy (Christopher Chang, Haijing Wu, Qianjin Lu)....Pages 141-152 Epigenetics and the Environment in Airway Disease: Asthma and Allergic Rhinitis (Andrew Long, Bryan Bunning, Vanitha Sampath, Rosemarie H. DeKruyff, Kari C. Nadeau)....Pages 153-181 Front Matter ....Pages 183-183 The Epigenetics of Lupus Erythematosus (Haijing Wu, Christopher Chang, Qianjin Lu)....Pages 185-207 Epigenetics of Psoriasis (Shuai Shao, Johann E. Gudjonsson)....Pages 209-221 The Role of Epigenetics in Type 1 Diabetes (Zhiguo Xie, Christopher Chang, Gan Huang, Zhiguang Zhou)....Pages 223-257 Epigenetics of Primary Biliary Cholangitis (Yikang Li, Ruqi Tang, Xiong Ma)....Pages 259-283 Epigenetics in Primary Sjögren’s Syndrome (Anne Bordron, Valérie Devauchelle-Pensec, Christelle Le Dantec, Arthur Capdeville, Wesley H. Brooks, Yves Renaudineau)....Pages 285-308 Epigenetics in Multiple Sclerosis (Vera Sau-Fong Chan)....Pages 309-374 The Epigenetic Regulation of Scleroderma and Its Clinical Application (Yangyang Luo, Rong Xiao)....Pages 375-403