Research Progress on the Immune-Related Pathogenesis and Treatment of Endometriosis

子宫内膜异位症免疫相关发病机制及治疗研究进展 Research Progress on the Immune-Related Pathogenesis and Treatment of Endometriosis Research Progress on the Immune-Related Pathogenesis and Treatment of Endometriosis DOI: 10.12677/ACM.2023.132374, PDF, 被引量 作者: 张 瑞, 陈志芳*：新疆医科大学第一附属医院，新疆 乌鲁木齐 关键词: 子宫内膜异位症；免疫学；发病机制；治疗；Endometriosis； Immunology； Pathogenesis； Treatment 作者: 张 瑞, 陈志芳*：新疆医科大学第一附属医院，新疆 乌鲁木齐 关键词: 子宫内膜异位症；免疫学；发病机制；治疗；Endometriosis； Immunology； Pathogenesis； Treatment 摘要: 子宫内膜异位症(endometriosis, EMs)是一种常见的慢性妇科疾病，其发病机制仍有争议，免疫力改变以及化生子宫内膜异位部位内的细胞因子是可能的关键因素。异位子宫内膜病理性生长是局部盆腔炎症过程，可导致某些免疫相关细胞的功能改变，这些细胞释放某些生长因子，导致子宫内膜斑块改变的进展。EMs类似于具有自身免疫背景和免疫抑制机制崩溃的免疫依赖性疾病。免疫学研究可能为发现EMs的创新免疫调节疗法开辟一条新途径。本文针对EMs相关免疫细胞功能及其改变、细胞因子、最新免疫治疗方法进行阐述，希望对进一步了解子宫内膜异位症发病机制及诊治提供帮助。 Abstract: Endometriosis (EMs) is a common chronic gynecological disease, and its pathogenesis is still con-troversial, and immune alteration and cytokines in metaplasia endometriosis sites are possible key factors. Ectopic pathological growth of the endometrium is a local pelvic inflammatory process that can lead to changes in the function of certain immune-related cells that release certain growth fac-tors, leading to the progression of endometrial plaque changes. EMs resembles an im-mune-dependent disease with an autoimmune background and collapse of immunosuppressive mechanisms. Immunology research may open up a new avenue for the discovery of innovative im-munomodulatory therapies for EMs. This article focuses on the function and changes of immune cells related to EMs, cytokines, and the latest immunotherapy methods, hoping to further under-stand the pathogenesis and diagnosis and treatment of EMs. 文章引用：张瑞, 陈志芳. 子宫内膜异位症免疫相关发病机制及治疗研究进展[J]. 临床医学进展, 2023, 13(2): 2643-2651. https://doi.org/10.12677/ACM.2023.132374 | [1] | 郎景和. 子宫内膜异位症和肿瘤: 兼论子宫内膜异位症恶变[J]. 中华妇产科杂志, 2019, 54(9): 577-581. | | [2] | Agostinis, C., Balduit, A., Mangogna, A., et al. (2021) Immunological Basis of the Endometriosis: The Complement System as a Potential Therapeutic Target. Frontiers in Immunology, 11, Article ID: 599117. [Google Scholar] [CrossRef] [PubMed] | | [3] | Moghaddam, M.Z., Ansariniya, H., Seifati, S.M., et al. (2022) Immunopathogenesis of Endometriosis: An Overview of the Role of Innate and Adaptive Immune Cells and Their Medi-ators. American Journal of Reproductive Immunology, 87, e13537. [Google Scholar] [CrossRef] [PubMed] | | [4] | Izumi, G., Koga, K., Takamura, M., et al. (2018) Involvement of Immune Cells in the Pathogenesis of Endometriosis. Journal of Obstetrics and Gynaecology Research, 44, 191-198. [Google Scholar] [CrossRef] [PubMed] | | [5] | Zhang, T., De Carolis, C., Man, G.C.W., et al. (2018) The Link between Immunity, Autoimmunity and Endometriosis: A Literature Update. Autoimmunity Reviews, 17, 945-955. [Google Scholar] [CrossRef] [PubMed] | | [6] | Barbe, A.M., Berbets, A.M., Davydenko, I.S., et al. (2020) Expression and Significance of Matrix Metalloproteinase-2 and Matrix Metalloproteinas-9 in Endometriosis. Journal of Medicine and Life, 13, 314-320. [Google Scholar] [CrossRef] [PubMed] | | [7] | Chen, S., Chai, X. and Wu, X. (2022) Bioinformatical Analysis of the Key Differentially Expressed Genes and Associations with Immune Cell Infiltration in Development of Endometriosis. BMC Genomic Data, 23, 20. [Google Scholar] [CrossRef] [PubMed] | | [8] | Wu, X.-G., Chen, J.-J., Zhou, H.-L., et al. (2021) Identification and Validation of the Signatures of Infiltrating Immune Cells in the Eutopic Endometrium Endometria of Women with Endometriosis. Frontiers in Immunology, 12, Article ID: 671201. [Google Scholar] [CrossRef] [PubMed] | | [9] | Vallvé-Juanico, J., Houshdaran, S. and Giudice, L.C. (2019) The Endometrial Immune Environment of Women with Endometriosis. Human Reproduction Update, 25, 564-591. [Google Scholar] [CrossRef] [PubMed] | | [10] | Li, L., Liao, Z., Ye, M., et al. (2021) Recombinant Human IL-37 In-hibited Endometriosis Development in a Mouse Model through Increasing Th1/Th2 Ratio by Inducing the Maturation of Dendritic Cells. Reproductive Biology and Endocrinology, 19, 128. [Google Scholar] [CrossRef] [PubMed] | | [11] | Tarokh, M., Ghaffari, N.M., Poordast, T., et al. (2019) Serum and Peritoneal Fluid Cytokine Profiles in Infertile Women with Endometriosis. Iranian Journal of Immunology, 16, 151-162. | | [12] | Yasuda, K., Takeuchi, Y. and Hirota, K. (2019) The Pathogenicity of Th17 Cells in Autoimmune Dis-eases. Seminars in Immunopathology, 41, 283-297. [Google Scholar] [CrossRef] [PubMed] | | [13] | Jiang, Y.-P., Peng, Y.-Q., Wang, L., et al. (2022) RNA-Sequencing Identifies Differentially Expressed Genes in T helper 17 Cells in Peritoneal Fluid of Patients with Endometriosis. Journal of Reproductive Immunology, 149, Article ID: 103453. [Google Scholar] [CrossRef] [PubMed] | | [14] | Jiang, Y.P., Wang, L., Peng, Y.Q., et al. (2022) Interleukin 17 Re-ceptor E Identifies Heterogeneous T Helper 17 Cells in Peritoneal Fluid of Moderate and Severe Endometriosis Patients. Clinical & Experimental Immunology, 207, 360-369. [Google Scholar] [CrossRef] [PubMed] | | [15] | Le Nhung, X.H., Loret de Mola Julio, R., Bremer, P., et al. (2021) Alteration of Systemic and Uterine Endometrial Immune Populations in Patients with Endometriosis. American Journal of Reproductive Immunology, 85, e13362. [Google Scholar] [CrossRef] [PubMed] | | [16] | Adur Malavika, K., Braundmeier-Fleming, A.G., Lessey, B.A., et al. (2021) Altered Eutopic Endometrial T-Regulatory and T-Helper 17 Lymphocyte Ratio in Women with Unexplained Subfertility. Journal of Endometriosis and Pelvic Pain Disorders, 13, 185-194. [Google Scholar] [CrossRef] [PubMed] | | [17] | Pashizeh, F., Mansouri, R., Davari-Tanha, F., et al. (2020) Al-terations of CD4+T Cell Subsets in Blood and Peritoneal Fluid in Different Stages of Endometriosis. International Jour-nal of Fertility and Sterility, 14, 201-208. | | [18] | 陈志刚, 阿曼古丽, 陈志芳, 李宏. 汉族和维吾尔族宫颈癌患者外周血CD4~+CD25~+调节性T细胞与TGF-β1及IL-10的表达及意义[J]. 当代医学, 2018, 24(31): 62-64. | | [19] | 陈志芳, 杜蓉, 韩英, 等. 维吾尔族宫颈癌人乳头瘤病毒感染与CD4~+CD25~+CD127~-调节性T细胞的相关性研究[J]. 实用妇产科杂志, 2011, 27(6): 439-443. | | [20] | Khan, K.N., Yamamoto, K., Fujishita, A., et al. (2019) Differential Levels of Regulatory T Cells and T-Helper-17 Cells in Women with Early and Advanced Endometriosis. The Journal of Clinical Endocrinology & Metabolism, 104, 4715-4729. [Google Scholar] [CrossRef] [PubMed] | | [21] | Olkowska-Truchanowicz, J., Sztokfisz-Ignasiak, A., Zwierzchowska, A., et al. (2021) Endometriotic Peritoneal Fluid Stimulates Recruitment of CD4+CD25highFOXP3+ Treg Cells. Journal of Clinical Medicine, 10, 3789. [Google Scholar] [CrossRef] [PubMed] | | [22] | Delbandi, A.A., Mahmoudi, M., Shervin, A., et al. (2020) Higher Fre-quency of Circulating, but Not Tissue Regulatory T Cells in Patients with Endometriosis. Journal of Reproductive Im-munology, 139, Article ID: 103119. [Google Scholar] [CrossRef] [PubMed] | | [23] | Rigby, C.H., Aljassim, F., Powell, S.G., et al. (2022) The Immune Cell Profile of Human Fallopian Tubes in Health and Benign Pathology: A Systematic Review. Journal of Reproductive Immunology, 152, Article ID: 103646. [Google Scholar] [CrossRef] [PubMed] | | [24] | Pashizeh, F., Mansouri, R., Davari-Tanha, F., et al. (2020) Altera-tions of CD4+T Cell Subsets in Blood and Peritoneal Fluid in Different Stages of Endometriosis. International Journal of Fertility and Sterility, 14, 201-208. | | [25] | Xiao, F.Y., Liu, X.S. and Guo, S.-W. (2020) Platelets and Regulatory T Cells May Induce a Type 2 Immunity That Is Conducive to the Progression and Fibrogenesis of Endometriosis. Frontiers in Immunology, 11, Article ID: 610963. [Google Scholar] [CrossRef] [PubMed] | | [26] | Kong, Y., Shao, Y., Ren, C.X., et al. (2021) Endometrial Stem/Progenitor Cells and Their Roles in Immunity, Clinical Application, and Endometriosis. Stem Cell Research & Therapy, 12, 474. [Google Scholar] [CrossRef] [PubMed] | | [27] | 董经纬, 苗柳. 巨噬细胞功能及其在心脏疾病中作用的研究进展[J]. 中国当代医药, 2022, 29(16): 49-52. | | [28] | García-Gómez, E., Vázquez-Martínez, E.R., Reyes-Mayoral, C., et al. (2020) Regulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis. Frontiers in Endocrinology (Lausanne), 10, 935. [Google Scholar] [CrossRef] [PubMed] | | [29] | Li, F., Alderman, M.H., Tal, A., et al. (2018) Hematogenous Dis-semination of Mesenchymal Stem Cells from Endometriosis. Stem Cells, 36, 881-890. [Google Scholar] [CrossRef] [PubMed] | | [30] | Gou, Y.L., Li, X., Li, P.L., et al. (2019) Estrogen Receptor β Upregulates CCL2 via NF-κB Signaling in Endometriotic Stromal Cells and Recruits Macrophages to Promote the Pathogenesis of Endometriosis. Human Reproduction, 34, 646-658. [Google Scholar] [CrossRef] [PubMed] | | [31] | 尹小瑞, 王莹东, 柳铮男, 等. 巨噬细胞在卵巢生理和病理情况下作用的研究进展[J]. 东南大学学报(医学版), 2021, 40(1): 119-124. | | [32] | Xie, Q., He, H., Wu, Y.H., et al. (2019) Eutopic Endometrium from Patients with Endometriosis Modu-lates the Expression of CD36 and SIRP-α in Peritoneal Macrophages. Journal of Obstetrics and Gynaecology Research, 45, 1045-1057. [Google Scholar] [CrossRef] [PubMed] | | [33] | Vallvé-Juanico, J., George, A.F., Sen, S., et al. (2022) Deep Immunophe-notyping Reveals Endometriosis Is Marked by Dysregulation of the Mononuclear Phagocytic System in Endometrium and Peripheral Blood. BMC Medicine, 20, 158. [Google Scholar] [CrossRef] [PubMed] | | [34] | 单婧, 王晓秋, 李大金. NK细胞参与子宫内膜异位症及其不孕的分子机制[J]. 山东大学学报(医学版), 2021, 59(8): 8-13. | | [35] | Shigesi, N., Kvaskoff, M., Kirtley, S., et al. (2019) The Association between Endometriosis and Autoimmune Diseases: A Systematic Review and Meta-Analysis. Human Reproduction Update, 25, 486-503. [Google Scholar] [CrossRef] [PubMed] | | [36] | Fukui, A., Mai, C.X., Saeki, S., et al. (2021) Pelvic Endometriosis and Natural Killer Cell Immunity. American Journal of Reproductive Immunology, 85, e13342. [Google Scholar] [CrossRef] [PubMed] | | [37] | Butterfield, J.H., Ravi, A. and Pongdee, T. (2018) Mast Cell Mediators of Significance in Clinical Practice in Mastocytosis. Immunology and Allergy Clinics of North America, 38, 397-410. [Google Scholar] [CrossRef] [PubMed] | | [38] | Borelli, V., Martinelli, M., Luppi, S., et al. (2020) Mast Cells in Per-itoneal Fluid from Women with Endometriosis and Their Possible Role in Modulating Sperm Function. Frontiers in Physiology, 10, 1543. [Google Scholar] [CrossRef] [PubMed] | | [39] | Li, T.T., Wang, J.Z., Guo, X.Y., et al. (2020) Possible Involvement of Crosstalk between Endometrial Cells and Mast Cells in the Development of Endometriosis via CCL8/CCR1. Biomedi-cine & Pharmacotherapy, 129, Article ID: 110476. [Google Scholar] [CrossRef] [PubMed] | | [40] | McCallion, A., Nasirzadeh, Y., Lingegowda, H., et al. (2022) Estrogen Mediates Inflammatory Role of Mast Cells in Endometriosis Pathophysiology. Frontiers in Immunology, 13, Article ID: 961599. [Google Scholar] [CrossRef] [PubMed] | | [41] | 曹立花, 李丽娟, 胡晓丹, 张晓钿. 姜黄素对子宫内膜异位症大鼠PI3K/AKT/GSK-3β通路及肥大细胞活化的影响[J]. 中国免疫学杂志, 2021, 37(4): 480-485. | | [42] | Symons, L.K., Miller, J.E., Kay, V.R., et al. (2018) The Immunopathophysiology of Endometriosis. Trends in Molecular Medicine, 24, 748-762. [Google Scholar] [CrossRef] [PubMed] | | [43] | Riccio, L.G.C., Santulli, P., Marcellin, L., et al. (2018) Immunology of Endometriosis. Best Practice & Research Clinical Obstetrics & Gynaecology, 50, 39-49. [Google Scholar] [CrossRef] [PubMed] | | [44] | Králíčkova, M., Fiala, L., Losan, P., et al. (2018) Altered Im-munity in Endometriosis: What Came First? Immunological Investigations, 47, 569-582. [Google Scholar] [CrossRef] [PubMed] | | [45] | 郭燕红, 杨利华, 张丽, 等. IL-17A对人子宫内膜异位症在位内膜细胞增殖的影响[J]. 免疫学杂志, 2021, 37(7): 624-628. | | [46] | Lukács, L., Kovács, A.R., Pál, L., et al. (2021) Phagocyte Function of Peripheral Neutrophil Granulocytes and Monocytes in Endometriosis before and after Surgery. Journal of Gynecology Obstetrics and Human Reproduction, 50, Article ID: 101796. [Google Scholar] [CrossRef] [PubMed] | | [47] | Suszczyk, D., Skiba, W., Zardzewiały, W., et al. (2022) Clinical Value of the PD-1/PD-L1/PD-L2 Pathway in Patients Suffering from Endometriosis. International Journal of Molecular Sciences, 23, Article ID: 11607. [Google Scholar] [CrossRef] [PubMed] | | [48] | 庄明燕, 金艳, 高军华. 异位子宫内膜组织中树突状细胞含量变化及其与免疫应答、细胞增殖侵袭的相关性[J]. 中国妇幼保健, 2019, 34(14): 3351-3353. | | [49] | 张统. 子宫内膜异位症内膜组织中树突状细胞的变化及其与蛋白酶表达、免疫应答的相关性[J]. 海南医学院学报, 2018, 24(20): 1813-1816. | | [50] | Jaeger-Lansky, A., Schmidthaler, K., Kuessel, L., et al. (2018) Local and Systemic Levels of Cyto-kines and Danger Signals in Endometriosis-Affected Women. Journal of Reproductive Immunology, 130, 7-10. [Google Scholar] [CrossRef] [PubMed] | | [51] | Zhou, W.-J., Yang, H.-L., Shao, J., et al. (2019) Anti-Inflammatory Cytokines in Endometriosis. Cellular and Molecular Life Sciences, 76, 2111-2132. [Google Scholar] [CrossRef] [PubMed] | | [52] | Samimi, M., Pourhanifeh, M.H., Mehdizadehkashi, A., et al. (2019) The Role of Inflammation, Oxidative Stress, Angiogenesis, and Apoptosis in the Pathophysiology of Endometri-osis: Basic Science and New Insights Based on Gene Expression. Journal of Cellular Physiology, 234, 19384-19392. [Google Scholar] [CrossRef] [PubMed] | | [53] | 朱定军, 叶梅. IL-6、IL-8、MCP-1和TNF-α在子宫内膜异位症诊断中的临床价值[J]. 中国生育健康杂志, 2019, 30(1): 53-56. | | [54] | Gueuvoghlanian-Silva, B.Y., Bellelis, P., Barbeiro, D.F., et al. (2018) Treg and NK Cells Related Cytokines Are Associated with Deep Rectosigmoid Endometriosis and Clinical Symptoms Related to the Disease. Journal of Reproductive Immunology, 126, 32-38. [Google Scholar] [CrossRef] [PubMed] | | [55] | Vanni, V.S., Villanacci, R., Salmeri, N., et al. (2021) Publisher Cor-rection: Concomitant Autoimmunity May Be a Predictor of More Severe Stages of Endometriosis. Scientific Reports, 11, Article No. 17715. [Google Scholar] [CrossRef] [PubMed] | | [56] | Kolanska, K., Alijotas-Reig, J., Cohen, J., et al. (2021) Endome-triosis with Infertility: A Comprehensive Review on the Role of Immune Deregulation and Immunomodulation Therapy. American Journal of Reproductive Immunology, 85, e13384. [Google Scholar] [CrossRef] [PubMed] | | [57] | Hecht, J., Su-liman, S. and Wegiel, B. (2021) Bacillus Calmette-Guerin (BCG) Vaccination to Treat Endometriosis. Vaccine, 39, 7353-7356. [Google Scholar] [CrossRef] [PubMed] | | [58] | Ścieżynska, A., Komorowski, M., Soszyńska, M. and Malejczyk, J. (2019) NK Cells as Potential Targets for Immunotherapy in Endometriosis. Journal of Clinical Medi-cine, 8, 1468. [Google Scholar] [CrossRef] [PubMed] | | [59] | Mathews, D.M., Johnson, N.P., Sim, R.G., et al. (2021) Iodine and Fertility: Do We Know Enough? Human Reproduction, 36, 265-274. [Google Scholar] [CrossRef] [PubMed] | | [60] | Peart, J.M., Sim, R.G. and Hofman, P.L. (2021) Therapeutic Effects of Hysterosalpingography Contrast Media in Infertile Women: What Do We Know about the H2O in the H2 Oil Trial and Why Does It Matter? Human Reproduction, 36, 529-535. [Google Scholar] [CrossRef] [PubMed] |