DNA vaccine, peripheral T-cell tolerance modulation 185

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Subject Index Airway hyperresponsiveness (AHR) animal models 41 43 asthma inhibition 45 overview 41 mast cell modulation of T-cells 62 64 respiratory tolerance 40, 41 Tregs inhibition role 44 respiratory tolerance role 40 roles 44, 45 Allergen-specific immunotherapy (SIT) asthma management 45 autoimmune disease 204, 205 B-cell regulation 165 dendritic cell regulation 165, 166 histamine and antihistamine roles 76 78 mechanisms 158, 159 peripheral T-cell tolerance antibody isotypes and effector cell suppression 162, 163 histamine receptors 169 171 mechanisms 159 162 Tregs activity induction 153, 154, 205 208 CD4 CD25 cells 164, 165 clinical relevance 168, 169 histamine receptors 170, 171 miscellaneous cells 165 suppression mechanisms 166 168 Th3 cells 164 Tr1 cells 163, 164 Allergic contact dermatitis, see Contact hypersensitivity Antigen-presenting cell, see B-cell; Dendritic cell; Langerhans cell; Macrophage Antihistamines, see Histamine Asthma airway hyperresponsiveness inhibition 45 overview 41 antihistamine therapy 72, 73, 77, 78 glucocorticoid receptor and T-cell-specific transcription factors 89 91 molecular targets for therapeutic intervention 84 T-box expressed in T-cells deficiency 87, 89 Treg interactions Th2 cells 85, 86 Th17 cells 86, 87 Atopic dermatitis tacrolimus therapy 195 T-cell regulation adaptive immune responses involving immunoglobulin E responses 102 aeroallergen-specific T-cells and eczematous responses 102, 103 autoantigen immune response 104 CD8 T-cells 105 cellular infiltrates 102 cytokine secretion and regulation 105 107 endothelium interactions 104 food-specific T-cells 103 221

Atopic dermatitis (continued) innate immune response defects 103 keratinocyte interactions 108, 109 microorganism activation 104 Th17 role 107 Treg role 107, 108 Autoimmune lymphoproliferative syndrome (ALPS), stem cell transplantation therapy 216 Basophil, allergy role 64 B-cell allergen-specific immunotherapy regulation 165 helminth parasite infection response 166, 117 histamine effects 76 Treg interactions 34, 35 CD8 T-cell, atopic dermatitis role 105 Contact hypersensitivity (CHS) animal model 94, 95 antigen-presenting cells 93 dendritic cell orchestration of skin immune response 97 99 Treg role 94 97 ultraviolet-b-induced immune tolerance 94 Dendritic cell (DC) allergen-specific immunotherapy regulation 165, 166 functional overview 189 fungal infection response 127, 128 histamine effects 74 lung cells activation and allergic inflammation and remodeling 192 195 allergic airway inflammation activity 191, 192 bridging of innate and adaptive immunity 190 therapeutic targeting 195, 196 tolerance induction 190, 191 Treg control 192 respiratory tolerance role 40 skin immune response orchestration 97 99 Treg interactions allergic and inflammatory reactions 35 37 dendritic cell maturation status and Treg induction potential 29, 30 suppression by Tregs 30 33 Diabetes mellitus type 1, stem cell transplantation therapy 215, 216 DNA vaccine, peripheral T-cell tolerance modulation 185 Eczema, see Atopic dermatitis Eosinophil, histamine effects 72 Experimental autoimmune encephalitis (EAE), antigen-based therapy 204 Foxp3 mutation and disease 22, 24, 96 transcriptional regulation Foxp3 22 Treg transcriptome 18 21 Treg expression 8, 9 roles development 18 function 17 FTY720, dendritic cell effects in allergic disease 195 Fungal infection adaptive immunity 128, 129 allergic diseases and features 124 126 dendritic cell response 127, 128 innate immunity 126, 127 pathogens 124 reverse and noncanonical signaling 133 135 Th17 response 129, 130 Th1/2 cell response 128, 129 Treg dampening of inflammation and allergy 130 133 tryptophan catabolism 133, 134 Glucocorticoids, asthma management and resistance 45, 89 91 Helminth parasite infection allergy and autoimmunity therapy lessons 120 autoimmune disease protection 115 epidemiology 112 115 immune regulation animal model studies 117, 118 B-cells 166, 117 innate immunity 119, 120 T-cells 115, 116, 118 treatment of inflammatory diseases 117 Histamine allergen-specific immunotherapy roles 76 78 antigen-presenting cell regulation 74 asthma and antihistamine therapy 72, 73, 77, 78 222 Subject Index

B-cell effects 76 chronic inflammatory responses 70 74 overview 67, 68 peripheral T-cell tolerance and receptors 169 171 receptors 68 70 regulatory/suppressor functions of HR2 161 synthesis and metabolism 70 T-cell effects 74 76 Immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome Foxp3 mutations 22, 24, 96 stem cell transplantation therapy 216, 217 Immunoglobulin E (IgE), monoclonal antibody therapy 186 Indoleamine 2,3-dioxygenase (IDO) fungal allergy regulation 133, 134 therapeutic targeting in asthma 84 Interferon- (IFN- ) delayed-type hypersensitivity suppression by ocular-induced CD8 Treg mediation 145, 146 therapeutic targeting in asthma 84, 91 Interleukin-6 (IL-6), bridging of innate and adaptive immunity 84, 85 Interleukin-10 (IL-10), T-cell anergy role 181, 182 Interleukin-25 (IL-25), inflammatory response in allergic diseases 183 Keratinocyte, T-cell interactions in atopic dermatitis 108, 109 Langerhans cell, mast cell priming of adaptive immune responses and allergic sensitization 59, 60 Lung dendritic cells, see Dendritic cell Macrophage histamine effects 74 Treg interactions 32 34 Mast cell functional overview 58, 59 priming of adaptive immune responses and allergic sensitization 59 62 T-cell modulation in airway hyperresponsiveness 62 64 Monocyte, see Macrophage Natural killer (NK) cell allergy role 53 55 cytokine profiles 50 53 inflammatory response in allergic diseases 183 lytic activity 50 receptors 50, 51 subsets 48 50 Neutrophil, histamine effects 72 Omalizumab, peripheral T-cell tolerance modulation 186 Peptide immunotherapy (PIT) peripheral T-cell tolerance regulation 162, 184, 205 Treg expansion 205 208 Peripheral T-cell tolerance aberrations in allergic disease 179, 181 allergen-specific immunotherapy antibody isotypes and effector cell suppression 162, 163 histamine receptors 169 171 mechanisms 159 162, 184 allergic inflammatory response pathobiology 178 180 immunotherapeutic approaches for regulation 183 186 inflammatory response in allergic diseases interleukin-25 183 natural killer cells 183 thymic stromal lymphopoietin 183 tumor necrosis factor- 182, 183 T-cell anergy 181, 182 Prostaglandin D 2, dendritic cell effects in allergic disease 195 Qa-1 b, restriction of delayed-type hypersensitivity suppression by ocular-induced CD8 Tregs 144, 145 Regulatory T cell, see Treg Retinoic acid, T-cell modulation 24 Rheumatoid arthritis (RA), stem cell transplantation therapy 215 Stem cell transplantation (SCT) autoimmune disorder management autoimmune lymphoproliferative syndrome 216 diabetes mellitus type 1 215, 216 Subject Index 223

Stem cell transplantation (SCT) (continued) immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome 216, 217 prospects 217, 218 rationale 213, 214 rheumatoid arthritis 215 systemic lupus erythematosus 214, 215 systemic sclerosis 215 goals 212, 213 overview 211, 212 safety and efficacy 213, 214 Systemic lupus erythematosus (SLE), stem cell transplantation therapy 214, 215 Systemic sclerosis, stem cell transplantation therapy 215 Tacrolimus, atopic dermatitis management 195 T-box expressed in T-cells (T-bet), deficiency in asthma 87, 89 Th1 cell cytokine profile 1, 2 differentiation 4, 5, 88 functional overview 2, 3 fungal infection response 128, 129 Th2 cell cytokine profile 1, 2 differentiation 4, 5, 88 functional overview 2, 3 fungal infection response 128, 129 Treg interactions in asthma 85, 86 Th17 cell atopic dermatitis role 107 cytokine profile 2 differentiation 4, 5, 88 fungal infection response 129, 130 inflammation role 4 Treg interactions in asthma 86, 87 Thymic stromal lymphopoietin (TSLP) inflammatory response in allergic diseases 183 lung dendritic cell maturation role 193, 194 Toll-like receptors (TLRs) fungal infection 126, 127, 134 Treg activity induction with ligands 154, 155 Transforming growth factor- (TGF- ) delayed-type hypersensitivity suppression by ocular-induced CD8 Treg mediation 146, 147 T-cell anergy role 181, 182 Treg airway hyperresponsiveness inhibition role 44 respiratory tolerance role 40 roles 44, 45 allergen-specific immunotherapy mediation activity induction 153, 154, 205 208 CD4 CD25 cells 164, 165 clinical relevance 168, 169 histamine receptors 170, 171 miscellaneous cells 165 suppression mechanisms 166 168 Th3 cells 164 Tr1 cells 163, 164 allergic disease inhibition induction of Treg activity allergen-specific immunotherapy 153, 154 Toll-like receptor ligands 154, 155 mechanisms 151 153 mouse models 151 therapeutic prospects 155, 156 allergy role 3, 4 antigen-presenting cell interactions B-cells 34, 35 dendritic cells allergic and inflammatory reactions 35 37 maturation status and Treg induction potential 29, 30 maturation suppression by Tregs 30 33 macrophages 32 34 atopic dermatitis role 107, 108 contact hypersensitivity modulation 94 97 development 9 12, 17, 18, 88, 150, 151 Foxp3 expression 8, 9 mutation and disease 22, 24, 96 roles development 18 function 17 transcriptional regulation Foxp3 22 Treg transcriptome 18 21 functional overview 2, 9, 12, 13 fungal infection and dampening of inflammation and allergy 130 133 heritable disorders 22, 24 histamine effects 74 76 lung dendritic cell control 192 224 Subject Index

natural resolution of autoimmune and allergic inflammation 202 204 natural versus induced cells 21, 22, 43, 44, 182 ocular-induced CD8 Tregs afferent and efferent mechanisms 141 143 anterior chamber-associated immune deviation 141 delayed-type hypersensitivity suppression animal studies 140, 141 antigen specificity 143, 144 interferon- mediation 145, 146 Qa-1 b restriction 144, 145 transforming growth factor- mediation 146, 147 overview 138, 139 suppressor activity 139, 140 products 2, 16 subtypes 83, 150 Th2 cell interactions 85, 86 therapeutic interventions 24 Tumor necrosis factor- (TNF- ), inflammatory response in allergic diseases 182, 183 VAF347, dendritic cell effects in allergic disease 196 Subject Index 225