Immunopathology of Endometriosis, Molecular Approaches

Immunopathology of Endometriosis, Molecular Approaches Sima Amidifar School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Search for more papers by this authorDavood Jafari Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Search for more papers by this authorAmir Hossein Mansourabadi Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada Brain and Mind Research Institute, University of Ottawa, Ottawa, Ontario, Canada Ottawa Hospital Research Institute, Ottawa, Ontario, Canada Search for more papers by this authorSara Sadaghian Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Search for more papers by this authorCorresponding Author Abdolreza Esmaeilzadeh Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran Correspondence: Abdolreza Esmaeilzadeh ([email protected]) Search for more papers by this authorSima Amidifar School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Search for more papers by this authorDavood Jafari Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Search for more papers by this authorAmir Hossein Mansourabadi Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada Brain and Mind Research Institute, University of Ottawa, Ottawa, Ontario, Canada Ottawa Hospital Research Institute, Ottawa, Ontario, Canada Search for more papers by this authorSara Sadaghian Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Search for more papers by this authorCorresponding Author Abdolreza Esmaeilzadeh Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran Correspondence: Abdolreza Esmaeilzadeh ([email protected]) Search for more papers by this authorABSTRACT Endometriosis (EMS) is a common chronic gynecological disorder affecting 5%–10% of reproductive-age women, often causing infertility, dyspareunia, pain, and limitations in physical and sexual activities. This condition is defined by the presence of endometrial tissue outside the uterus, commonly explained by Sampson's theory of retrograde menstruation. Although its etiology remains unclear, genetic, epigenetic, hormonal imbalances, oxidative stress, and immune factors play critical roles. Immune dysregulation, involving inflammatory factors, cytokines, and immune cells facilitates the implantation, proliferation, angiogenesis, and development of ectopic endometrial stromal cells (ESCs). Research indicates that the implantation of ESCs in the peritoneum triggers an inflammatory response, recruiting various immune cells and leading to a cycle of inflammation characterized by elevated growth factors and cytokines. In this review, we discuss the immune system's role in EMS pathogenesis, emphasizing the contributions of immune cells, inflammatory mediators, oxidative stress, and so forth. This review also highlights that while current treatments, including hormonal therapies and surgical interventions, aim to alleviate symptoms and improve fertility, emerging evidence suggests that advancements in immunotherapies targeting specific immune cell activities hold promise as innovative future treatment strategies enhancing healthcare management for affected women. Conflicts of Interest The authors declare no conflicts of interest. Data Availability Statement The data that support the findings of this study are available from the corresponding author upon reasonable request. References - 1Y. H. Lin, Y. H. Chen, H. Y. Chang, H. K. Au, C. R. Tzeng, and Y. H. Huang, “Chronic Niche Inflammation in Endometriosis-Associated Infertility: Current Understanding and Future Therapeutic Strategies,” International Journal of Molecular Sciences 19, no. 8 (2018): 2385, https://doi.org/10.3390/ijms19082385. - 2E. Pašalić, M. M. Tambuwala, and A. Hromić-Jahjefendić, “Endometriosis: Classification, Pathophysiology, and Treatment Options,” Pathology, Research and Practice 251 (2023): 154847, https://doi.org/10.1016/j.prp.2023.154847. - 3M. Y. Lee, S. H. Kim, Y. S. Oh, et al., “Role of Interleukin-32 in the Pathogenesis of Endometriosis: In Vitro, Human and Transgenic Mouse Data,” Human Reproduction 33, no. 5 (2018): 807–816, https://doi.org/10.1093/humrep/dey055. - 4P. A. B. Klemmt and A. Starzinski-Powitz, “Molecular and Cellular Pathogenesis of Endometriosis,” Current Women's Health Reviews 14, no. 2 (2018): 106–116, https://doi.org/10.2174/1573404813666170306163448. - 5C. Chapron, M.-C. Lafay-Pillet, E. Monceau, et al., “Questioning Patients About Their Adolescent History Can Identify Markers Associated With Deep Infiltrating Endometriosis,” Fertility and Sterility 95, no. 3 (2011): 877–881. - 6C. Chapron, L. Marcellin, B. Borghese, and P. Santulli, “Rethinking Mechanisms, Diagnosis and Management of Endometriosis,” Nature Reviews Endocrinology 15, no. 11 (2019): 666–682. - 7H. Kobayashi, “Proposal for Adenomyosis Classification Based on the Endometriosis Phenotype,” Medical Hypotheses 158 (2022): 110742. - 8S. Maruyama, S. Imanaka, M. Nagayasu, M. Kimura, and H. Kobayashi, “Relationship Between Adenomyosis and Endometriosis; Different Phenotypes of a Single Disease?” European Journal of Obstetrics & Gynecology and Reproductive Biology 253 (2020): 191–197. - 9V. Balasubramanian, R. Saravanan, L. D. Joseph, et al., “Molecular Dysregulations Underlying the Pathogenesis of Endometriosis,” Cellular Signalling 88 (2021): 110139. - 10B. G. Patel, E. E. Lenk, D. I. Lebovic, Y. Shu, J. Yu, and R. N. Taylor, “Pathogenesis of Endometriosis: Interaction Between Endocrine and Inflammatory Pathways,” Best Practice & Research Clinical Obstetrics & Gynaecology 50 (2018): 50–60. - 11T. Blamble and L. Dickerson, “Recognizing and Treating Endometriosis,” JAAPA 34, no. 6 (2021): 14–19. - 12L. K. Symons, J. E. Miller, V. R. Kay, et al., “The Immunopathophysiology of Endometriosis,” Trends in Molecular Medicine 24, no. 9 (2018): 748–762. - 13L. Jiang, Y. Yan, Z. Liu, and Y. Wang, “Inflammation and Endometriosis,” Frontiers in Bioscience (Landmark Ed) 21, no. 5 (2016): 941–948. - 14H. Jørgensen, A. S. Hill, M. T. Beste, et al., “Peritoneal Fluid Cytokines Related to Endometriosis in Patients Evaluated for Infertility,” Fertility and Sterility 107, no. 5 (2017): 1191–1199, https://doi.org/10.1016/j.fertnstert.2017.03.013. - 15V. S. Baranov, T. E. Ivaschenko, T. Liehr, and M. I. Yarmolinskaya, “Systems Genetics View of Endometriosis: A Common Complex Disorder,” European Journal of Obstetrics, Gynecology, and Reproductive Biology 185 (2015): 59–65, https://doi.org/10.1016/j.ejogrb.2014.11.036. - 16I. N. A. Azam, N. A. Wahab, M. H. Mokhtar, M. N. Shafiee, and N. M. Mokhtar, “Roles of microRNAs in Regulating Apoptosis in the Pathogenesis of Endometriosis,” Life (Basel) 12, no. 9 (2022): 1321, https://doi.org/10.3390/life12091321. - 17S. P. Monsanto, A. K. Edwards, J. Zhou, et al., “Surgical Removal of Endometriotic Lesions Alters Local and Systemic Proinflammatory Cytokines in Endometriosis Patients,” Fertility and Sterility 105, no. 4 (2016): 968–977.e5, https://doi.org/10.1016/j.fertnstert.2015.11.047. - 18W.-N. Li, M.-H. Wu, and S.-J. Tsai, “Critical Factors Involved in Chronic Inflammation in the Pathophysiology of Endometriosis,” Adaptive Medicine 10, no. 1 (2018): 1–9. 10.4247/AM.2018.ABI197Google Scholar - 19O. Taskin, K. Rikhraj, J. Tan, T. Sedlak, T. C. Rowe, and M. A. Bedaiwy, “Link Between Endometriosis, Atherosclerotic Cardiovascular Disease, and the Health of Women Midlife,” Journal of Minimally Invasive Gynecology 26, no. 5 (2019): 781–784. - 20V. M. Vazgiourakis, M. I. Zervou, L. Papageorgiou, et al., “Association of Endometriosis With Cardiovascular Disease: Genetic Aspects (Review),” International Journal of Molecular Medicine 51, no. 3 (2023): 29, https://doi.org/10.3892/ijmm.2023.5232. - 21K. Arumugam and J. M. Lim, “Menstrual Characteristics Associated With Endometriosis,” BJOG: An International Journal of Obstetrics & Gynaecology 104, no. 8 (1997): 948–950. - 22A. Ashish, K. Kusum, S. Rai, and R. Singh, “Endometriosis a Brief Review: Evaluation of Crucial Risk Factors and Current Treatment Regimes,” International Journal of Advanced Medicine 7, no. 12 (2020): 1896. 10.18203/2349-3933.ijam20205053Google Scholar - 23F. Ji, X. Yang, Y. He, H. Wang, A. Aili, and Y. Ding, “Aberrant Endometrial DNA Methylome of Homeobox A10 and Catechol-O-Methyltransferase in Endometriosis,” Journal of Assisted Reproduction and Genetics 34 (2017): 409–415. - 24B. R. Mason, D. Chatterjee, C. O. Menias, P. H. Thaker, C. L. Siegel, and M. Yano, “Encyclopedia of Endometriosis: A Pictorial Rad-Path Review,” Abdominal Radiology 45 (2020): 1587–1607. - 25D. Van den Nouland and M. Kaur, “Primary Umbilical Endometriosis: A Case Report,” Facts, Views & Vision in Obstetrics and Gynecology 9, no. 2 (2017): 115. - 26A. Augoulea, I. Lambrinoudaki, and G. Christodoulakos, “Thoracic Endometriosis Syndrome,” Respiration 75, no. 1 (2008): 113–119, https://doi.org/10.1159/000105102. - 27E. Evans-Hoeker, B. A. Lessey, J. W. Jeong, et al., “Endometrial BCL6 Overexpression in Eutopic Endometrium of Women With Endometriosis,” Reproductive Science 23, no. 9 (2016): 1234–1241, https://doi.org/10.1177/1933719116649711. - 28C. Amalinei, I. Păvăleanu, L. Lozneanu, R. Balan, S.-E. Giuşcă, and I.-D. Căruntu, “Endometriosis—Insights Into a Multifaceted Entity,” Folia Histochemica Et Cytobiologica 56, no. 2 (2018): 61–82. - 29S. Liu, G. Liu, L. Yang, D. Li, and M. Zheng, “Critical Influences of Metal Compounds on the Formation and Stabilization of Environmentally Persistent Free Radicals,” Chemical Engineering Journal 427 (2022): 131666. - 30R. Z. Zhao, S. Jiang, L. Zhang, and Z. B. Yu, “Mitochondrial Electron Transport Chain, ROS Generation and Uncoupling,” International Journal of Molecular Medicine 44, no. 1 (2019): 3–15. - 31L. Feng and J. Lou, “DNA Methylation Analysis,” Nanotoxicity: Methods and Protocols 1894 (2019): 181–227. 10.1007/978-1-4939-8916-4_12Google Scholar - 32L.dG. C. Riccio, P. Santulli, L. Marcellin, M. S. Abrão, F. Batteux, and C. Chapron, “Immunology of Endometriosis,” Best Practice & Research Clinical Obstetrics & Gynaecology 50 (2018): 39–49. - 33Y. Wang, K. Nicholes, and I. M. Shih, “The Origin and Pathogenesis of Endometriosis,” Annual Review of Pathology 15 (2020): 71–95, https://doi.org/10.1146/annurev-pathmechdis-012419-032654. - 34M. Králíčková and V. Vetvicka, “Immunological Aspects of Endometriosis: A Review,” Annals of Translational Medicine 3, no. 11 (2015): 153, https://doi.org/10.3978/j.issn.2305-5839.2015.06.08. - 35P. C. A. Crispim, M. P. Jammal, E. F. C. Murta, and R. S. Nomelini, “Endometriosis: What Is the Influence of Immune Cells?” Immunological Investigations 50, no. 4 (2021): 372–388, https://doi.org/10.1080/08820139.2020.1764577. - 36G. Izumi, K. Koga, M. Takamura, et al., “Involvement of Immune Cells in the Pathogenesis of Endometriosis,” Journal of Obstetrics and Gynaecology Research 44, no. 2 (2018): 191–198, https://doi.org/10.1111/jog.13559. - 37J. G. Cronin, V. Kanamarlapudi, C. A. Thornton, and I. M. Sheldon, “Signal Transducer and Activator of Transcription-3 Licenses Toll-Like Receptor 4-Dependent Interleukin (IL)-6 and IL-8 Production via IL-6 Receptor-Positive Feedback in Endometrial Cells,” Mucosal Immunology 9, no. 5 (2016): 1125–1136, https://doi.org/10.1038/mi.2015.131. - 38S. A. Hoseinian, D. Jafari, M. Mahmoodi, et al., “The Impact of Donor and Recipient KIR Genes and KIR Ligands on the Occurrence of Acute Graft-Versus-Host Disease and Graft Survival After HLA-Identical Sibling Hematopoietic Stem Cell Transplantation,” Turkish Journal of Medical Sciences 48, no. 4 (2018): 794–804, https://doi.org/10.3906/sag-1712-75. - 39D. Jafari, M. Nafar, M. S. Yekaninejad, et al., “Investigation of Killer Immunoglobulin-Like Receptor (KIR) and HLA Genotypes to Predict the Occurrence of Acute Allograft Rejection After Kidney Transplantation,” Iranian Journal of Allergy, Asthma and Immunology 16, no. 3 (2017): 245–255. - 40K. K. Chang, L. B. Liu, L. P. Jin, et al., “IL-27 Triggers IL-10 Production in Th17 Cells via a c-Maf/RORγt/Blimp-1 Signal to Promote the Progression of Endometriosis,” Cell Death & Disease 8, no. 3 (2017): e2666, https://doi.org/10.1038/cddis.2017.95. - 41R. Galandrini, M. G. Porpora, A. Stoppacciaro, et al., “Increased Frequency of Human Leukocyte Antigen–E Inhibitory Receptor CD94/NKG2A–Expressing Peritoneal Natural Killer Cells in Patients With Endometriosis,” Fertility and Sterility 89, no. 5 (2008): 1490–1496. - 42N. Maeda, C. Izumiya, Y. Yamamoto, H. Oguri, T. Kusume, and T. Fukaya, “Increased Killer Inhibitory Receptor KIR2DL1 Expression Among Natural Killer Cells in Women with Pelvic Endometriosis,” Fertility and Sterility 77, no. 2 (2002): 297–302. - 43H. Xu, “Expressions of Natural Cytotoxicity Receptor, NKG2D and NKG2D Ligands in Endometriosis,” Journal of Reproductive Immunology 136 (2019): 102615. - 44L. Wu, C. Lv, Y. Su, et al., “Expression of Programmed Death-1 (PD-1) and Its Ligand PD-L1 Is Upregulated in Endometriosis and Promoted by 17beta-Estradiol,” Gynecological Endocrinology 35, no. 3 (2019): 251–256. - 45M. R. Rached, V. Coelho, M. L. C. Marin, et al., “HLA-G Is Upregulated in Advanced Endometriosis,” European Journal of Obstetrics & Gynecology and Reproductive Biology 235 (2019): 36–41. - 46D. Suszczyk, W. Skiba, J. Jakubowicz-Gil, J. Kotarski, and I. Wertel, “The Role of Myeloid-Derived Suppressor Cells (MDSCs) in the Development and/or Progression of Endometriosis-State of the Art,” Cells 10, no. 3 (2021): 677, https://doi.org/10.3390/cells10030677. - 47J. O. Jin, W. Zhang, J. Y. Du, and Q. Yu, “BDCA1-positive Dendritic Cells (DCs) Represent a Unique Human Myeloid DC Subset That Induces Innate and Adaptive Immune Responses to Staphylococcus aureus Infection,” Infection and Immunity 82, no. 11 (2014): 4466–4476, https://doi.org/10.1128/IAI.01851-14. - 48D. Szukiewicz, “Epigenetic Regulation and T-cell Responses in Endometriosis—Something Other Than Autoimmunity,” Frontiers in Immunology 13 (2022): 943839, https://doi.org/10.3389/fimmu.2022.943839. - 49C. Mehedintu, M. N. Plotogea, S. Ionescu, and M. Antonovici, “Endometriosis Still a Challenge,” Journal of Medicine and Life 7, no. 3 (2014): 349–357. - 50S. Vallcaneras, F. Ghersa, J. Bastón, M. B. Delsouc, G. Meresman, and M. Casais, “TNFRp55 Deficiency Promotes the Development of Ectopic Endometriotic-Like Lesions in Mice,” Journal of Endocrinology 234, no. 3 (2017): 269–278, https://doi.org/10.1530/JOE-17-0236. - 51H. Valizadeh, S. Abdolmohammadi-Vahid, S. Danshina, et al., “Nano-Curcumin Therapy, a Promising Method in Modulating Inflammatory Cytokines in COVID-19 Patients,” International Immunopharmacology 89, no. Pt B (2020): 107088, https://doi.org/10.1016/j.intimp.2020.107088. - 52A. Funamizu, A. Fukui, M. Kamoi, et al., “Expression of Natural Cytotoxicity Receptors on Peritoneal Fluid Natural Killer Cell and Cytokine Production by Peritoneal Fluid Natural Killer Cell in Women With Endometriosis,” American Journal of Reproductive Immunology 71, no. 4 (2014): 359–367. - 53S. Abdullah, R. H. Sørensen, and F. E. Nielsen, “Prognostic Accuracy of SOFA, qSOFA, and SIRS for Mortality Among Emergency Department Patients With Infections,” Infection and Drug Resistance 14 (2021): 2763–2775, https://doi.org/10.2147/IDR.S304952. - 54E. A. Elewa, O. Zakaria, E. I. Mohamed, and G. Boghdadi, “The Role of Interleukins 4, 17 and Interferon Gamma as Biomarkers in Patients With Systemic Lupus Erythematosus and Their Correlation with Disease Activity,” Egyptian Rheumatologist 36, no. 1 (2014): 21–27. 10.1016/j.ejr.2013.10.003Google Scholar - 55A. D. Keegan, W. J. Leonard, and J. Zhu, “Recent Advances in Understanding the Role of IL-4 Signaling,” Faculty Reviews 10 (2021): 71, doi:10.12703/r/10-71. - 56D. Imani, R. Rezaei, D. Jafari, et al., “IL-6 174 G/C Polymorphism in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis,” Acta Medica Iranica 56, no. 12 (2018): 740–749. - 57M. E. Manesh, A. Esmaeilzadeh, and M. H. Mirzaei, “IL-24: A Novel Gene Therapy Candidate for Immune System Upregulation in Hodgkin's Lymphoma,” Journal of Medical Hypotheses and Ideas 9, no. 1 (2015): 61–66. 10.1016/j.jmhi.2014.05.002Google Scholar - 58X.-M. Wang, Z.-Y. Ma, and N. Song, “Inflammatory Cytokines IL-6, IL-10, IL-13, TNF-α and Peritoneal Fluid Flora Were Associated With Infertility in Patients With Endometriosis,” European Review for Medical & Pharmacological Sciences 22, no. 9 (2018): 2513–2518. - 59M. E. Meniailo, V. V. Malashchenko, V. A. Shmarov, et al., “Interleukin-8 Favors Pro-Inflammatory Activity of Human Monocytes/Macrophages,” International Immunopharmacology 56 (2018): 217–221. - 60K. Koga, Y. Osuga, O. Yoshino, et al., “Elevated Interleukin-16 Levels in the Peritoneal Fluid of Women With Endometriosis May Be a Mechanism for Inflammatory Reactions Associated with Endometriosis,” Fertility and Sterility 83, no. 4 (2005): 878–882. - 61J. Zhang, W. Zhao, Y. Zhou, et al., “Pyroptotic T Cell-Derived Active IL-16 Has a Driving Function in Ovarian Endometriosis Development,” Cell Reports Medicine 5, no. 3 (2024): 101476, https://doi.org/10.1016/j.xcrm.2024.101476. - 62E. Khosh, N. Bahmaie, R. Elahi, and A. Esmaeilzadeh, “Clinical Applications of Interleukin-37; as a Key Player in the Immunopathogenesis of Immune Disorders,” Iranian Journal of Allergy, Asthma and Immunology 19, no. 3 (2020): 209–228. - 63S. Moghadam, M. Erfanmanesh, and A. Esmaeilzadeh, “Interleukin 35 and Hepatocyte Growth Factor; as a Novel Combined Immune Gene Therapy for Multiple Sclerosis Disease,” Medical Hypotheses 109 (2017): 102–105, https://doi.org/10.1016/j.mehy.2017.09.017. - 64J. E. Miller, S. P. Monsanto, S. H. Ahn, et al., “Interleukin-33 Modulates Inflammation in Endometriosis,” Scientific Reports 7, no. 1 (2017): 17903, https://doi.org/10.1038/s41598-017-18224-x. - 65X. Li, X. Liu, and W. Wang, “IL-35: A Novel Immunomodulator in Hepatitis B Virus-Related Liver Diseases,” Frontiers in Cell and Developmental Biology 9 (2021): 614847, https://doi.org/10.3389/fcell.2021.614847. - 66C. Zhang, Z. Peng, D. Ban, and Y. Zhang, “Upregulation of Interleukin 35 in Patients With Endometriosis Stimulates Cell Proliferation,” Reproductive Sciences 25, no. 3 (2018): 443–451, https://doi.org/10.1177/1933719117715123. - 67J. Jiang, K. Yu, Z. Jiang, and M. Xue, “IL-37 Affects the Occurrence and Development of Endometriosis by Regulating the Biological Behavior of Endometrial Stromal Cells through Multiple Signaling Pathways,” Biological Chemistry 399, no. 11 (2018): 1325–1337, https://doi.org/10.1515/hsz-2018-0254. - 68R. B. Maksym, M. Hoffmann-Mlodzianowska, M. Skibinska, M. Rabijewski, A. Mackiewicz, and C. Kieda, “Immunology and Immunotherapy of Endometriosis,” Journal of Clinical Medicine 10, no. 24 (2021), https://doi.org/10.3390/jcm10245879. - 69Y. Li, X. Lv, M. Jiang, and Z. Jin, “Sitagliptin Ameliorates Hypoxia-Induced Damages in Endometrial Stromal Cells: An Implication in Endometriosis,” Bioengineered 13, no. 1 (2022): 800–809, https://doi.org/10.1080/21655979.2021.2012950. - 70M. A. Schneider, M. Linecker, R. Fritsch, et al., “Phase Ib Dose-Escalation Study of the Hypoxia-Modifier Myo-Inositol Trispyrophosphate in Patients With Hepatopancreatobiliary Tumors,” Nature Communications 12, no. 1 (2021): 3807, https://doi.org/10.1038/s41467-021-24069-w. - 71J. Shi, X. Tan, G. Feng, et al., “Research Advances in Drug Therapy of Endometriosis,” Frontiers in Pharmacology 14 (2023): 1199010, https://doi.org/10.3389/fphar.2023.1199010. - 72S. Rafique and A. H. Decherney, “Medical Management of Endometriosis,” Clinical Obstetrics and Gynecology 60, no. 3 (2017): 485–496, https://doi.org/10.1097/GRF.0000000000000292. - 73T. Genovese, R. Siracusa, R. D'Amico, et al., “Regulation of Inflammatory and Proliferative Pathways by Fotemustine and Dexamethasone in Endometriosis,” International Journal of Molecular Sciences 22, no. 11 (2021): 5998, https://doi.org/10.3390/ijms22115998. - 74W. J. Zhou, H. L. Yang, J. Shao, et al., “Anti-Inflammatory Cytokines in Endometriosis,” Cellular and Molecular Life Sciences 76, no. 11 (2019): 2111–2132, https://doi.org/10.1007/s00018-019-03056-x. - 75J. Hecht, S. Suliman, and B. Wegiel, “Bacillus Calmette-Guerin (BCG) Vaccination to Treat Endometriosis,” Vaccine 39, no. 50 (2021): 7353–7356, https://doi.org/10.1016/j.vaccine.2021.07.020. - 76Q. Liu, Y. Tian, X. Zhao, et al., “NMAAP1 Expressed in BCG-Activated Macrophage Promotes M1 Macrophage Polarization,” Molecules and Cells 38, no. 10 (2015): 886–894, doi:10.14348/molcells.2015.0125. - 77W. Li, A. Lin, L. Qi, et al., “Immunotherapy: A Promising Novel Endometriosis Therapy,” Frontiers in Immunology 14 (2023): 1128301, https://doi.org/10.3389/fimmu.2023.1128301. - 78S. Podgaec, M. S. Abrao, J. A. Dias Jr, L. V. Rizzo, R. M. de Oliveira, and E. C. Baracat, “Endometriosis: An Inflammatory Disease With a Th2 Immune Response Component,” Human Reproduction 22, no. 5 (2007): 1373–1379, https://doi.org/10.1093/humrep/del516. - 79A. Sciezynska, M. Komorowski, M. Soszynska, and J. Malejczyk, “NK Cells as Potential Targets for Immunotherapy in Endometriosis,” Journal of Clinical Medicine 8, no. 9 (2019): 1468, https://doi.org/10.3390/jcm8091468. - 80J. L. Reis, N. N. Rosa, M. Angelo-Dias, C. Martins, L. M. Borrego, and J. Lima, “Natural Killer Cell Receptors and Endometriosis: A Systematic Review,” International Journal of Molecular Sciences 24, no. 1 (2022): 331, https://doi.org/10.3390/ijms24010331. - 81L. Li, Z. Liao, M. Ye, and J. Jiang, “Recombinant human IL-37 Inhibited Endometriosis Development in a Mouse Model Through Increasing Th1/Th2 Ratio by Inducing the Maturation of Dendritic Cells,” Reproductive Biology and Endocrinology [Electronic Resource]: RB&E 19, no. 1 (2021): 128, https://doi.org/10.1186/s12958-021-00811-3. - 82M. Ichioka, S. Mita, Y. Shimizu, et al., “Dienogest, a Synthetic Progestin, Down-Regulates Expression of CYP19A1 and Inflammatory and Neuroangiogenesis Factors through Progesterone Receptor Isoforms A and B in Endometriotic Cells,” Journal of Steroid Biochemistry and Molecular Biology 147 (2015): 103–110, https://doi.org/10.1016/j.jsbmb.2014.12.008. - 83H. J. Kim, S. H. Kim, Y. S. Oh, S. R. Lee, and C. HD, “Dienogest May Reduce Estradiol- and Inflammatory Cytokine-Induced Cell Viability and Proliferation and Inhibit the Pathogenesis of Endometriosis: A Cell Culture- and Mouse Model-Based Study,” Biomedicines 10, no. 11 (2022): 2992, https://doi.org/10.3390/biomedicines10112992. - 84G. Grandi, M. Mueller, N. A. Bersinger, A. Cagnacci, A. Volpe, and B. McKinnon, “Does Dienogest Influence the Inflammatory Response of Endometriotic Cells? A Systematic Review,” Inflammation Research 65, no. 3 (2016): 183–192, https://doi.org/10.1007/s00011-015-0909-7. - 85Y. Liu, H. Gong, J. Gou, X. Liu, and Z. Li, “Dienogest as a Maintenance Treatment for Endometriosis Following Surgery: A Systematic Review and Meta-Analysis,” Frontiers in Medicine (Lausanne) 8 (2021): 652505, https://doi.org/10.3389/fmed.2021.652505. - 86K. Yamanaka, B. Xu, I. Suganuma, et al., “Dienogest Inhibits Aromatase and Cyclooxygenase-2 Expression and Prostaglandin E(2) Production in Human Endometriotic Stromal Cells in Spheroid Culture,” Fertility and Sterility 97, no. 2 (2012): 477–482, https://doi.org/10.1016/j.fertnstert.2011.11.005. - 87W. Waiyaput, K. Wattanakamolchai, Y. Tingthanatikul, et al., “Effect of Combined Contraceptive Pill on Immune Cell of Ovarian Endometriotic Tissue,” Journal of Ovarian Research 14, no. 1 (2021): 66, https://doi.org/10.1186/s13048-021-00819-8. - 88L. Cui, X. Shao, W. Sun, et al., “Anti-Inflammatory Effects of Progesterone Through NF-kappaB and MAPK Pathway in Lipopolysaccharide- or Escherichia coli-stimulated Bovine Endometrial Stromal Cells,” PLoS ONE 17, no. 4 (2022): e0266144, https://doi.org/10.1371/journal.pone.0266144. - 89T. A. Fedotcheva, N. I. Fedotcheva, and N. L. Shimanovsky, “Progesterone as an Anti-Inflammatory Drug and Immunomodulator: New Aspects in Hormonal Regulation of the Inflammation,” Biomolecules 12, no. 9 (2022): 1299, https://doi.org/10.3390/biom12091299. 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