Th17/Treg比例失衡与卵巢衰老

doi:10.12280/gjszjk.20250477

摘要/Abstract

摘要：

卵巢衰老分为生理性与病理性两类，表现为卵巢储备功能下降、卵泡数量减少和激素水平紊乱，并与多种慢性疾病风险相关。研究发现，免疫失衡在卵巢衰老中扮演核心角色，尤其是辅助性T细胞17（helper T cell 17，Th17细胞）与调节性T细胞（regulatory T cell，Treg细胞）的比例失调。Th17/Treg平衡受炎症因子、核因子κB（nuclear factor-κB，NF-κB）通路及哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）通路的精密调控，其失衡会加剧卵巢局部炎症，加速卵泡耗竭。目前，针对Th17/Treg比例失衡的干预策略在自身免疫性疾病的治疗中已取得进展，为卵巢衰老的临床干预提供了新思路。综述Th17/Treg比例失衡在卵巢衰老中的核心作用，为探索延缓卵巢衰老的免疫治疗策略提供了理论依据。

关键词: Th17细胞, T淋巴细胞，调节性, 免疫调节, 卵巢衰老, 细胞失衡

Abstract:

Ovarian aging is divided into the physiological and pathological categories, characterized by decreased ovarian reserve function, reduced follicle numbers, and hormonal imbalances. Ovarian aging is associated with the risk of various chronic diseases. Research has found that immune imbalance plays a central role in ovarian aging, particularly the dysregulation of the ratio between helper T cell 17 (Th17 cell) and regulatory T cell (Treg cell). The Th17/Treg balance is precisely regulated by inflammatory factors, nuclear factor-κB (NF-κB) pathway, and mammalian target of rapamycin (mTOR) pathway. Its imbalance exacerbates ovarian local inflammation and accelerates follicular depletion. Currently, intervention strategies targeting the Th17/Treg imbalance have made progress in the treatment of autoimmune diseases, providing new approaches for clinical intervention in ovarian aging. We review the critical role of Th17/Treg imbalance in ovarian aging, offering a theoretical basis for the formulation of immunotherapy strategies to postpone ovarian aging.

Key words: Th17 cells, T-lymphocytes, regulatory, Immunomodulation, Ovarian aging, Cellular imbalance

张俊荣, 陈潜力, 成曦, 徐云钊. Th17/Treg比例失衡与卵巢衰老[J]. 国际生殖健康/计划生育杂志, 2026, 45(1): 54-59.

ZHANG Jun-rong, CHEN Qian-li, CHENG Xi, XU Yun-zhao. The Correlation between Th17/Treg Ratio Imbalance and Ovarian Aging[J]. Journal of International Reproductive Health/Family Planning, 2026, 45(1): 54-59.

参考文献 31

[1]	Wang Y, Kong F, Fu Y, et al. How can China tackle its declining fertility rate?[J]. BMJ, 2024, 386:e078635. doi: 10.1136/bmj-2023-078635.
[2]	Benayoun BA, Kochersberger A, Garrison JL. Studying ovarian aging and its health impacts: modern tools and approaches[J]. Genes Dev, 2025, 39(15/16):975-990. doi: 10.1101/gad.352732.125.
[3]	Hense JD, Isola J, Garcia DN, et al. The role of cellular senescence in ovarian aging[J]. NPJ Aging, 2024, 10(1):35. doi: 10.1038/s41514-024-00157-1. pmid: 39033161
[4]	Zeng Y, Wang C, Yang C, et al. Unveiling the role of chronic inflammation in ovarian aging: insights into mechanisms and clinical implications[J]. Hum Reprod, 2024, 39(8):1599-1607. doi: 10.1093/humrep/deae132.
[5]	Gao H, Gao L, Wang W. Advances in the cellular immunological pathogenesis and related treatment of primary ovarian insufficiency[J]. Am J Reprod Immunol, 2022, 88(5):e13622. doi: 10.1111/aji.13622.
[6]	Cheng H, Nan F, Ji N, et al. Regulatory T cell therapy promotes TGF-β and IL-6-dependent pro-inflammatory Th17 cell generation by reducing IL-2[J]. Nat Commun, 2025, 16(1):7644. doi: 10.1038/s41467-025-62628-7.
[7]	Park E, Ciofani M. Th17 cell pathogenicity in autoimmune disease[J]. Exp Mol Med, 2025, 57(9):1913-1927. doi: 10.1038/s12276-025-01535-9. pmid: 40887501
[8]	Nouri N, Aghebati-Maleki L, Soltani-Zangbar MS, et al. Analysis of Th17 cell population and expression of microRNA and factors related to Th17 in patients with premature ovarian failure[J]. J Reprod Immunol, 2024, 165:104290. doi: 10.1016/j.jri.2024.104290.
[9]	Roy P, Orecchioni M, Ley K. How the immune system shapes atherosclerosis: roles of innate and adaptive immunity[J]. Nat Rev Immunol, 2022, 22(4):251-265. doi: 10.1038/s41577-021-00584-1.
[10]	Zhou S, Huang J, Zhang Y, et al. Exosomes in Action: Unraveling Their Role in Autoimmune Diseases and Exploring Potential Therapeutic Applications[J]. Immune Netw, 2024, 24(2):e12. doi: 10.4110/in.2024.24.e12. pmid: 38725675
[11]	Wang J, Zhao X, Wan YY. Intricacies of TGF-β signaling in Treg and Th17 cell biology[J]. Cell Mol Immunol, 2023, 20(9):1002-1022. doi: 10.1038/s41423-023-01036-7. pmid: 37217798
[12]	Zou D, Li XC, Chen W. Beyond T-cell subsets: stemness and adaptation redefining immunity and immunotherapy[J]. Cell Mol Immunol, 2025, 22(9):957-974. doi: 10.1038/s41423-025-01321-7. pmid: 40634636
[13]	Xiao C, Zhao X, Hu Z, et al. MFSD2A Overexpression Inhibits Hepatocellular Carcinoma Through TGF-β/Smad Signaling[J]. Mol Carcinog, 2025, 64(3):597-611. doi: 10.1002/mc.23875.
[14]	O'Connor JL, Nissen JC. The Pathological Activation of Microglia Is Modulated by Sexually Dimorphic Pathways[J]. Int J Mol Sci, 2023, 24(5):4739. doi: 10.3390/ijms24054739.
[15]	Daniels MA, Teixeiro E. The NF-κB signaling network in the life of T cells[J]. Front Immunol, 2025, 16:1559494. doi: 10.3389/fimmu.2025.1559494.
[16]	Zhao Y, Yu C, Sun H, et al. Exploring the causal link between serum 25-hydroxyvitamin D concentrations and idiopathic sudden sensorineural hearing loss: Insights gained from a Mendelian randomization study involving two independent samples[J]. PLoS One, 2025, 20(5):e0322898. doi: 10.1371/journal.pone.0322898.
[17]	Duan X, Lv X, Wang X, et al. Impact of immune cell metabolism on membranous nephropathy and prospective therapy[J]. Commun Biol, 2025, 8(1):405. doi: 10.1038/s42003-025-07816-3. pmid: 40065158
[18]	Xu W, Chen H, Xiao H. mTORC2: A neglected player in aging regulation[J]. J Cell Physiol, 2024, 239(11):e31363. doi: 10.1002/jcp.31363.
[19]	Wang Z, Xu Z, Zong M, et al. Metabolic regulation of Th17 and Treg cell balance by the mTOR signaling[J]. Metabol Open, 2025, 26:100369. doi: 10.1016/j.metop.2025.100369.
[20]	Wu L, Kensiski A, Gavzy SJ, et al. Rapamycin immunomodulation utilizes time-dependent alterations of lymph node architecture, leukocyte trafficking, and gut microbiome[J]. JCI Insight, 2025, 10(8):e186505. doi: 10.1172/jci.insight.186505.
[21]	Zhou C, Guo Q, Lin J, et al. Single-Cell Atlas of Human Ovaries Reveals The Role Of The Pyroptotic Macrophage in Ovarian Aging[J]. Adv Sci(Weinh), 2024, 11(4):e2305175. doi: 10.1002/advs.202305175.
[22]	Zhang Z, Schlamp F, Huang L, et al. Inflammaging is associated with shifted macrophage ontogeny and polarization in the aging mouse ovary[J]. Reproduction, 2020, 159(3):325-337. doi: 10.1530/REP-19-0330.
[23]	Yousefzadeh MJ, Flores RR, Zhu Y, et al. An aged immune system drives senescence and ageing of solid organs[J]. Nature, 2021, 594(7861):100-105. doi: 10.1038/s41586-021-03547-7.
[24]	Lliberos C, Liew SH, Zareie P, et al. Evaluation of inflammation and follicle depletion during ovarian ageing in mice[J]. Sci Rep, 2021, 11(1):278. doi: 10.1038/s41598-020-79488-4. pmid: 33432051
[25]	Ma L, Lu H, Chen R, et al. Identification of Key Genes and Potential New Biomarkers for Ovarian Aging: A Study Based on RNA-Sequencing Data[J]. Front Genet, 2020, 11:590660. doi: 10.3389/fgene.2020.590660.
[26]	Yang Y, Li H, Zuo J, et al. Mechanistic Interactions Driving Nucleus Pulposus Cell Senescence in Intervertebral Disc Degeneration: A Multi-Axial Perspective of Mechanical, Immune, and Metabolic Pathways[J]. JOR Spine, 2025, 8(3):e70089. doi: 10.1002/jsp2.70089.
[27]	Liao R, Zhao P, Wu J, et al. Salidroside protects against intestinal barrier dysfunction in septic mice by regulating IL-17 to block the NF-κB and p38 MAPK signaling pathways[J]. Exp Ther Med, 2023, 25(2):89. doi: 10.3892/etm.2023.11788.
[28]	Khattri S, González-Cantero Á, Engin B, et al. Comparative Effectiveness of Biologic Classes in Clinical Practice: Month 12 Outcomes from the International Observational Psoriasis Study of Health Outcomes (PSoHO)[J]. Adv Ther, 2025, 42(1):233-245. doi: 10.1007/s12325-024-03034-1. pmid: 39520657
[29]	Xiang Y, Wang H, Ding H, et al. Hyperandrogenism drives ovarian inflammation and pyroptosis: A possible pathogenesis of PCOS follicular dysplasia[J]. Int Immunopharmacol, 2023, 125(Pt A):111141. doi: 10.1016/j.intimp.2023.111141.
[30]	Jean Wilson E, Sirpu Natesh N, Ghadermazi P, et al. Red Cabbage Juice-Mediated Gut Microbiota Modulation Improves Intestinal Epithelial Homeostasis and Ameliorates Colitis[J]. Int J Mol Sci, 2023, 25(1):539. doi: 10.3390/ijms25010539.
[31]	Fang F, A T, Chen J, et al. Therapeutic potential of regulatory T cells for stem cell regulation: Insights from Treg-mediated enhancement of limbal stem cell functions[J]. iScience, 2025, 28(5):112515. doi: 10.1016/j.isci.2025.112515.