Immunology of Endometriosis: Pathogenesis and Management

Front Cover
IMMUNOLOGY OF ENDOMETRIOSIS
About the Series
IMMUNOLOGY OF ENDOMETRIOSIS: PATHOGENESIS AND MANAGEMENT
Copyright
Reproductive immunology
Contents
List of contributors
About the series editor
About the editor
Preface
I -  Immune factors in the pathogenesis, and the potential therapeutic target, of endometriosis
	1 - B lymphocytes
		Increased B lymphocyte number and activation
		The role of antibodies
		Endometriosis: an autoimmune disease?
		Future perspectives in treating endometriosis
		References
	2 - Macrophages in endometriosis: they came, they saw, they conquered
		Introduction
		Macrophage origins and phenotype
		Physiological roles of macrophages: same cell, many different occupations
			Professional phagocyte and antigen presenter
			The “healer”
			The “caretaker”
			The “shaper”
		Factors affecting macrophage activity
		Role of macrophages in disease
		Macrophages in endometriosis
			Endometrial macrophages are elevated during menses: seeds for new soil?
			Ectopic endometrium: a new land for colonization
			Ectopic endometrial lesions as wounds: a perpetual battleground
			Macrophages promote urbanization once the new land has been colonized
			Local climate impacts macrophage behavior
			Macrophages and endometriosis-associated infertility: a hostile habitat
		Summary
		References
	3 - Dendritic cells
		Introduction
		DC population in endometriosis patients
		Plasmacytoid dendritic cell
		Animal study using endometriosis mouse models
		Molecular target on dendritic cells
		Discussion
		References
	4 - Neutrophils
		Introduction
		Neutrophil abundance and dysregulated function in endometriosis
			Neutrophil chemokines
			Neutrophil in peripheral blood and candidate for disease marker
			Dysregulated function of neutrophils in endometriosis
		Findings obtained from animal model
		Putative therapeutic targets
			Cabergoline
			Formyl peptide receptor 1 (Fpr1)
			Cyclooxygenase (COX)-2 inhibitor
			All-transretinoic acid (ATRA)
			Other candidate related to neutrophil function
		References
	5 - Role of Th1, Th2, Th17, and regulatory T cells in endometriosis
		Introduction
		Cross talk between innate immunity and adaptive immunity
		Role of innate immunity in endometriosis
			Microbial agents, ligands and TLRs
			Subclinical infection as source of initial inflammation
			LPS/TLR4/NF-kB in endometriosis: an experimental evidence
			Association between ovarian steroids and immune cells
		Role of adaptive (acquired) immunity in endometriosis
			Th1/Th2 cells in endometriosis
			Th17/Treg cells in endometriosis
		Treg cells in ovarian endometrioma and nonendometrioma
			Occurrence of peritoneal lesions in women with ovarian endometrioma and nonendometrioma
			FoxP3+Treg cells in ovarian endometrioma and dermoid cysts
			FoxP3+Treg cells in endometria based on phases of the menstrual cycle
			FoxP3+Treg cells based on the color appearance of peritoneal lesions
			TGF-beta/IL-6 in PF of women with or without peritoneal lesions
		Role of activated Treg cells in endometriosis: human and animal study
			CD45RA−FoxP3high activated Treg cells in human endometriosis
			A model of temporary depletion of Treg cells in mice
			Changes in endometriosis-like lesions and inflammation in Treg cell ablated mice
		Treg/Th17 cells in early and advanced endometriosis
			Treg/Th17 cells in PF/PF of early and advanced endometriosis
			Treg/Th17 cells in PB/PF based on the phases of menstrual cycle
			Treg/Th17 cells based on the color appearance of peritoneal lesions
			Comparison of Treg cells and effector T cells in PB and PF
			TGF-beta/IL-17 levels in PF of early and advanced endometriosis
		Summary and perspective
		References
	6 - Auto-immunity and endometriosis: evidence, mechanism and therapeutic potential
		Introduction
		The association between endometriosis and autoimmune diseases
		Autoimmune-related mechanisms in endometriosis
			Humoral-mediated immunity
				Immunological abnormalities in B cell
				Autoantibodies associated with infertility
			Immunological abnormalities in T cell function
		Estrogen related immune response in autoimmune diseases and endometriosis
		Autoimmune-related genetics in endometriosis
		Potential immunomodulatory therapy for autoimmunity in endometriosis
			Hormonal therapies
			Immunomodulatory therapy
				Anti-TNF-α therapies
				Pentoxifylline
				Vitamin D
		Conclusion
		References
	7 - Role of estrogen and estrogen-related factors in endometriosis
		Introduction
		Estrogen production in endometriosis (Fig. 7.1)
		Aromatase regulation in endometriosis
		Transcriptional regulation of aromatase expression in endometriosis
		Aromatase targeting as a treatment option for endometriosis
		Estrogen receptors in endometriosis
			Classical estrogen receptors in endometriosis
			GPER in endometriosis
			Estrogen-related receptors in endometriosis
		Summary and perspective
		Acknowledgments
		References
	8 - Hypoxia and immune factors
		Introduction (immunology in endometriosis)
		The role of hypoxia in the pathogenesis of endometriosis
		Hypoxia modulates immune responses in endometriosis
			Proinflammatory cytokines
			Immune cells
		Regulation of HIF-1α by immune factors
		The potential approaches for therapy
		Conclusion
		References
	9 - The roles and functions of macrophages in endometriosis
		Background
		The origin, activation, subtype, and biological function of macrophages
		Macrophage recruitment, polarization and their corresponding activating factors
		Roles and functions of macrophages in endometriosis
			Inflammation
				Inflammation and macrophages
				The interaction between inflammation and macrophages
			Angiogenesis
			Estrogen biosynthesis
			Endometriosis-associated pain
				Macrophages and neurogenesis
				Interaction between macrophages and nerve fibers
			Fibrogenesis
		Potential therapeutic targets regarding macrophages
		Conclusions and future perspectives
		Acknowledgments
		References
II - The role of immune factors in endometriosis-related conditions
	10 - Pain
		Introduction
		Hormonal and inflammatory microenvironment in endometriosis: a vicious circle
		Pathogenesis of inflammation in endometriotic implants
		Neurogenesis in endometriotic implants
		Immune system and neuroangiogenesis: a bidirectional signaling mechanism
		The role of drug therapy in immunomodulation of pain
		References
	11 - Immune phenotypes and mediators affecting endometrial function in women with endometriosis
		Introduction
		Immune cells in endometrium of women with endometriosis
			Innate immune system
			Adaptive immune system
			Steroid hormone dependence
		Proinflammatory endometrial environment in women with endometriosis
			Immune cells
				Macrophages (Mϕ)
				Dendritic cells (DCs)
				Mast cells (MCs)
				Regulatory T cells (Treg)
			Nonimmune cells
				Microbial environment
				Endometrial epithelial cells
				Endometrial stromal fibroblasts (eSF)
				Endometrial mesenchymal stem cells
			Cytokines and chemokines
				Proinflammatory milieu
				Interleukin-1 (IL-1)
				Interleukin-6 (IL-6)
				Interleukin-8 (IL-8 or CXCL8)
				Tumor necrosis factor alpha (TNF-α)
				RANTES (CCL5)
				Monocyte chemoattractant protein 1 (MCP-1/CCL2)
				Eotaxin (CCL11)
				Interleukin 11 (IL-11)
		Role of endometrial cells in endometriosis pathogenesis and tissue function/dysfunction
			Endometriosis pathogenesis
			Tissue shedding
			Dysmenorrhea and pelvic pain
			Tissue regeneration and repair
			Implications for pregnancy
				Immune cells
				Nonimmune cells
		Conclusions
		References
	12 - Endometriosis and ovarian dysfunction
		Introduction
		Functional structure and cellular components of human ovary and endometriosis
		Histological alteration of ovarian cortex in women with endometriosis: burn-out hypothesis
		Dysregulation of ovarian functions in endometriosis and clinical consequences in infertility therapy
		Immunocomplexome analysis of follicular fluids of women with endometriosis
		Conclusions
		References
	13 - The role of immune-related redox biology in malignant transformation of endometriosis
		Introduction
		Immune dysfunction linked to endometriosis development and malignant transformation
		The recruitment and phenotype of macrophages in endometriosis and its malignant transformation
		The role of oxidative stress in endometriosis and its malignant transformation
		The role of antioxidant property in endometriosis and its malignant transformation
		Mechanism underlying malignant transformation of endometriosis
		Conclusion
		Acknowledgments
		References
	14 - Pregnancy complications
		Pathogenesis of the relationship between endometriosis and pregnancy
			Decidualization
			Compromised decidualization in case of endometriosis
			Decidualization of ectopic lesions
		Impact of pregnancy on endometriosis symptoms
		Impact of endometriosis on pregnancy outcomes
			Miscarriage
			Preterm birth
			Intrauterine growth retardation, low birth weight and small for gestational age
			Hypertensive disease
			Placenta abnormalities
			Cesarean section
		Surgical endometriosis-related complication during pregnancy
			Spontaneous hemoperitoneum in pregnancy
			Uterine rupture
			Urinary tract complications
			Bowel complications
		Conclusion
		References
III - Immunology and the management of endometriosis
	15 - Prevalent innate and adaptive immune mechanisms in endometriosis
		Introduction
		The dynamic immune landscape in the eutopic endometrium
		Prominent roles of macrophages in endometrial-associated inflammation
		Macrophage activation paradigms
		Macrophages are major constituents of the endometriotic lesion-immune microenvironment
		T lymphocytes: adaptive immune roles in endometriosis
		The role of B cells and correlative autoimmune features in endometriosis
		The endocrine-immune interface in endometriosis
		Immunomodulatory therapeutic opportunities and future of endometriosis management
		References
	16 - Novel therapeutic strategy: antiinflammatory reagents: Role of NF-κB in endometriosis
		Introduction
		The NF-ΚB signaling pathway
		NF-ΚB expression in normal endometrium
		NF-ΚB expression in women with endometriosis
		The role of NF-KB to promote inflammation in endometriosis
		NF-ΚB and macrophages
		NF-ΚB regulates cox-2 and prostaglandin expression
		NF-ΚB and angiogenesis
		Future perspective focused on the NF-ΚB pathway for the treatment of endometriosis
		References
	17 - Gut microbiota and endometriosis
		General remarks
			Microbiota
			Dysbiosis
			Diversity of microbiomes: α-diversity, β-diversity, and F/B ratio
		Endometriosis and microbiome
			Estrogen and microbiome
			Helper T cells (Th1, Th2, Th17, and regulatory T cells) and microbiome
				Th1/Th2 cells
				Th17 cells
				Treg cells
		Data of gut microbiota in endometriosis
			Human endometriosis
			Animal endometriosis model
		Conclusion
		References
	18 - Immunosuppression and immunotherapy in endometriosis: review of pathophysiology, recent development and future ...
		Introduction
		Immunosuppressive network in endometriosis (Table 18.1, Fig. 18.1)
			Immunosuppressive immune cell in endometriosis
			Immunosuppressive cytokines and growth factors
			Other immunosuppressive factors
		Immune microenvironment
			Endometrial cells adhesion, angiogenesis, proliferation
			Epithelial-mesenchymal transition
		Therapies in endometriosis
			Current therapies in endometriosis
			Immunotherapy (Table 18.2)
			Cytokine-mediated therapy
			Cell-based therapy
			Future perspectives: personalized and combination therapy
		Conclusions
		References
	19 - Novel diagnostic strategies for endometriosis
		Introduction
			What is a noninvasive diagnostic test for endometriosis?
			Which noninvasive tests show the most promise?
		Surgical diagnosis of endometriosis
		Imaging modalities for the noninvasive diagnosis of endometriosis
		Blood biomarkers for the noninvasive diagnosis of endometriosis
		Endometrial biomarkers for the noninvasive diagnosis of endometriosis
		Urinary biomarkers for the noninvasive diagnosis of endometriosis
		Combination of the noninvasive tests for the diagnosis of endometriosis
		Conclusion
		References
Index
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	T
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	X
	Y
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