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Medical Diagnosis 2026
TH17细胞和Treg细胞在梅毒血清固定发病机制中的作用
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Abstract:
人们对梅毒的自然历史了解很多，但对梅毒血清固定的发病机制的了解不够深入，由于梅毒在中国的患病率不断上升，血清固定率也出现了较大的增长，然而梅毒血清固定的发生机制尚不明确，而且患者的临床预后往往存在多种不确定因素，因此血清固定已经成为梅毒的预防和控制，尤其是临床诊断和治疗所面临的疑难问题。目前有研究表明梅毒血清固定和多种因素有关，比如梅毒螺旋体的免疫原性，临床因素，体液免疫，细胞免疫和免疫失衡。特别地，细胞免疫中的Th17细胞的免疫作用以及它与Treg细胞失衡在梅毒血清固定的发病机制中扮演着重要角色。
People have a lot of knowledge about the natural history of syphilis, but the understanding of the pathogenesis of syphilis serofast is not deep enough. Due to the rising prevalence of syphilis in China, the serofast rate has also increased greatly. However, the pathogenesis of syphilis serofast is not clear, and there are many uncertain factors in the clinical prognosis of patients. Therefore, serofast has become a difficult problem in the prevention and control of syphilis, especially in clinical diagnosis and treatment. At present, studies have shown that syphilis serofast is related to a variety of factors, such as the immunogenicity of Treponema pallidum, clinical factors, humoral immunity, cellular immunity and immune imbalance. In particular, the immune function of Th17 cells in cellular immunity and its imbalance with Treg cells play an important role in the pathogenesis of syphilis seroresistance. This article reviews the role of Th17 cells in the pathogenesis of serofast syphilis.
| [1] | Chen, Q., Wu, W., Wang, L., Huang, H. and Wang, L. (2025) Symptomatic Neurosyphilis in HIV-Negative Patients: A Retrospective Cohort Study. Frontiers in Public Health, 13, Article 1505818. https://doi.org/10.3389/fpubh.2025.1505818 |
| [2] | Bathobakae, L., Russo, J., Bashir, R., Vidreiro, A., Phuu, P., Wilkinson, T., et al. (2024) Novelty in the Gut: A Review of the Gastrointestinal Manifestations of Syphilis. Scandinavian Journal of Gastroenterology, 59, 1306-1313. https://doi.org/10.1080/00365521.2024.2429676 |
| [3] | Arisawa, Y., Sugawara, K., Morioka, H. and Takada, K. (2024) Syphilis Showing Multiple Pulmonary Nodules without Respiratory Symptoms. Internal Medicine, 63, 885-886. https://doi.org/10.2169/internalmedicine.1754-23 |
| [4] | Chen, T., Wan, B., Wang, M., Lin, S., Wu, Y. and Huang, J. (2023) Evaluating the Global, Regional, and National Impact of Syphilis: Results from the Global Burden of Disease Study 2019. Scientific Reports, 13, Article No. 11386. https://doi.org/10.1038/s41598-023-38294-4 |
| [5] | Sankaran, D., Partridge, E. and Lakshminrusimha, S. (2023) Congenital Syphilis—An Illustrative Review. Children, 10, Article 1310. https://doi.org/10.3390/children10081310 |
| [6] | Peeling, R.W., Mabey, D., Chen, X. and Garcia, P.J. (2023) Syphilis. The Lancet, 402, 336-346. https://doi.org/10.1016/s0140-6736(22)02348-0 |
| [7] | Tao, Y., Chen, M.Y., Tucker, J.D., Ong, J.J., Tang, W., Wong, N.S., et al. (2019) A Nationwide Spatiotemporal Analysis of Syphilis over 21 Years and Implications for Prevention and Control in China. Clinical Infectious Diseases, 70, 136-139. https://doi.org/10.1093/cid/ciz331 |
| [8] | Li, J., Yang, Y., Huang, B. and Zeng, J. (2024) Epidemiological Characteristics of Syphilis in Mainland China, 2004 to 2019. Journal of International Medical Research, 52. https://doi.org/10.1177/03000605241258465 |
| [9] | 周平玉. 梅毒血清固定再认识[J]. 中华皮肤科杂志, 2017, 50(5): 379-381. |
| [10] | Tong, M., Lin, L., Liu, G., Zhang, H., Zeng, Y., Zheng, W., et al. (2013) Factors Associated with Serological Cure and the Serofast State of HIV-Negative Patients with Primary, Secondary, Latent, and Tertiary Syphilis. PLOS ONE, 8, e70102. https://doi.org/10.1371/journal.pone.0070102 |
| [11] | Lin, L., Zheng, W., Tong, M., Fu, Z., Liu, G., Fu, J., et al. (2011) Further Evaluation of the Characteristics of Treponema pallidum-Specific IgM Antibody in Syphilis Serofast Reaction Patients. Diagnostic Microbiology and Infectious Disease, 71, 201-207. https://doi.org/10.1016/j.diagmicrobio.2011.07.005 |
| [12] | 闫薇臣, 吴捷, 林昌炎, 等. 免疫功能与梅毒血清固定的相关性研究[J]. 医学信息, 2024, 37(13): 106-109. |
| [13] | Cheng, W., Lu, Y., Chen, R., Ren, H. and Hu, W. (2021) Decreased Blood Natural Killer Cells in Serofast Patients: A Systematic Review and Meta-analysis. Central European Journal of Immunology, 46, 509-515. https://doi.org/10.5114/ceji.2021.111540 |
| [14] | 温晶, 李珍, 赵伟, 等. 梅毒血清固定患者外周血Th1,Th2,Treg和Th17相关细胞因子检测[J]. 中国麻风皮肤病杂志, 2021, 37(6): 356-359. |
| [15] | Sena, A.C., Wolff, M., Behets, F., Van Damme, K., Martin, D.H., Leone, P., et al. (2012) Response to Therapy Following Retreatment of Serofast Early Syphilis Patients with Benzathine Penicillin. Clinical Infectious Diseases, 56, 420-422. https://doi.org/10.1093/cid/cis918 |
| [16] | Ren, R., Wang, L., Zheng, H. and Li, J. (2015) No Improvement in Serological Response among Serofast Latent Patients Retreated with Benzathine Penicillin. International Journal of STD & AIDS, 27, 58-62. https://doi.org/10.1177/0956462415573677 |
| [17] | 林小记, 朱青玉. 综合性心理干预对梅毒血清固定患者焦虑、抑郁情绪及生活质量的影响[J]. 皮肤病与性病, 2020, 42(4): 513-514. |
| [18] | Mills, K.H.G. (2022) IL-17 and Il-17-Producing Cells in Protection versus Pathology. Nature Reviews Immunology, 23, 38-54. https://doi.org/10.1038/s41577-022-00746-9 |
| [19] | Alexander, M.D., Meyers, P.M., English, J.D., Stradford, T.R., Sung, S., Smith, W.S., et al. (2014) Symptom Differences and Pretreatment Asymptomatic Interval Affect Outcomes of Stenting for Intracranial Atherosclerotic Disease. American Journal of Neuroradiology, 35, 1157-1162. https://doi.org/10.3174/ajnr.a3836 |
| [20] | Bedoya, S.K., Lam, B., Lau, K. and Larkin, J. (2013) Th17 Cells in Immunity and Autoimmunity. Clinical and Developmental Immunology, 2013, Article ID: 986789. https://doi.org/10.1155/2013/986789 |
| [21] | Yu, F., Sharma, S., Edwards, J., Feigenbaum, L. and Zhu, J. (2014) Dynamic Expression of Transcription Factors T-Bet and GATA-3 by Regulatory T Cells Maintains Immunotolerance. Nature Immunology, 16, 197-206. https://doi.org/10.1038/ni.3053 |
| [22] | Ovcinnikovs, V., Ross, E.M., Petersone, L., Edner, N.M., Heuts, F., Ntavli, E., et al. (2019) CTLA-4-Mediated Transendocytosis of Costimulatory Molecules Primarily Targets Migratory Dendritic Cells. Science Immunology, 4, eaaw0902. https://doi.org/10.1126/sciimmunol.aaw0902 |
| [23] | Sawant, D.V., Yano, H., Chikina, M., Zhang, Q., Liao, M., Liu, C., et al. (2019) Adaptive Plasticity of IL-10+ and IL-35+Treg Cells Cooperatively Promotes Tumor T Cell Exhaustion. Nature Immunology, 20, 724-735. https://doi.org/10.1038/s41590-019-0346-9 |
| [24] | Cao, X., Cai, S.F., Fehniger, T.A., Song, J., Collins, L.I., Piwnica-Worms, D.R., et al. (2007) Granzyme B and Perforin Are Important for Regulatory T Cell-Mediated Suppression of Tumor Clearance. Immunity, 27, 635-646. https://doi.org/10.1016/j.immuni.2007.08.014 |
| [25] | Keir, M.E., Butte, M.J., Freeman, G.J. and Sharpe, A.H. (2008) PD-1 and Its Ligands in Tolerance and Immunity. Annual Review of Immunology, 26, 677-704. https://doi.org/10.1146/annurev.immunol.26.021607.090331 |
| [26] | 陈丹, 李智铭, 林建新, 等. 梅毒血清固定患者外周血中Th17/Treg细胞、Foxp3和ROR-γt的表达水平及相关性研究[J]. 北京医学, 2017, 39(11): 1146-1149. |
| [27] | Meng, Q., Li, Z., Huang, Z., Chen, N., Lin, W., Zhong, Y., et al. (2025) Recombinant Protein TprK Promotes M1 Macrophage Polarization and Phagocytosis by Inducing Indoleamine 2,3-Dioxygenase Protein Production. Biochimica et Biophysica Acta (BBA)—Molecular Cell Research, 1872, Article ID: 120005. https://doi.org/10.1016/j.bbamcr.2025.120005 |
| [28] | Zhou, L., Lopes, J.E., Chong, M.M.W., Ivanov, I.I., Min, R., Victora, G.D., et al. (2008) TGF-β-Induced Foxp3 Inhibits TH17 Cell Differentiation by Antagonizing RORγt Function. Nature, 453, 236-240. https://doi.org/10.1038/nature06878 |
| [29] | Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T.B., Oukka, M., et al. (2006) Reciprocal Developmental Pathways for the Generation of Pathogenic Effector TH17 and Regulatory T Cells. Nature, 441, 235-238. https://doi.org/10.1038/nature04753 |
| [30] | Wang, C., Zhu, L., Gao, Z., Guan, Z., Lu, H., Shi, M., et al. (2014) Increased Interleukin-17 in Peripheral Blood and Cerebrospinal Fluid of Neurosyphilis Patients. PLOS Neglected Tropical Diseases, 8, e3004. https://doi.org/10.1371/journal.pntd.0003004 |
| [31] | Zhao, W. and Luo, H. (2023) Investigation of the Role of Interleukin 27 in the Immune Regulation of Treg and Th17 Cells in Neurosyphilis Patients. Folia Neuropathologica, 61, 387-395. https://doi.org/10.5114/fn.2023.132099 |
| [32] | 关杨, 吴肖冰, 郑锦芬, 等. 梅毒血清固定患者外周血CD4+CD25+叉状头螺旋转录因子+调节性T细胞及其相关因子的表达[J]. 临床皮肤科杂志, 2021, 50(6): 326-330. |
| [33] | Yang, L., Anderson, D.E., Baecher-Allan, C., Hastings, W.D., Bettelli, E., Oukka, M., et al. (2008) IL-21 and TGF-β Are Required for Differentiation of Human TH17 Cells. Nature, 454, 350-352. https://doi.org/10.1038/nature07021 |
| [34] | Huang, G., Wang, Y. and Chi, H. (2012) Regulation of TH17 Cell Differentiation by Innate Immune Signals. Cellular & Molecular Immunology, 9, 287-295. https://doi.org/10.1038/cmi.2012.10 |
| [35] | Huang, X.K., Yang, Q.T., Chen, Y.L. and Zhang, G.H. (2014) Correlation of γδ-T-Cells, Th17 Cells and IL-17 in Peripheral Blood of Patients with Allergic Rhinitis. Asian Pacific Journal of Allergy and Immunology, 32, 235-239. |
| [36] | Ouyang, X., Zhang, R., Yang, J., Li, Q., Qin, L., Zhu, C., et al. (2011) Transcription Factor IRF8 Directs a Silencing Programme for TH17 Cell Differentiation. Nature Communications, 2, Article No. 314. https://doi.org/10.1038/ncomms1311 |
| [37] | Lee, S., Moon, J., Lee, A.R., Moon, Y., Choi, J.W., Lee, C.R., et al. (2025) mtSTAT3 Suppresses Rheumatoid Arthritis by Regulating Th17 and Synovial Fibroblast Inflammatory Cell Death with Il-17-Mediated Autophagy Dysfunction. Experimental & Molecular Medicine, 57, 221-234. https://doi.org/10.1038/s12276-024-01376-y |
| [38] | Kurebayashi, Y., Nagai, S., Ikejiri, A. and Koyasu, S. (2013) Recent Advances in Understanding the Molecular Mechanisms of the Development and Function of th17 Cells. Genes to Cells, 18, 247-265. https://doi.org/10.1111/gtc.12039 |
| [39] | 王江, 赵雪妍, 方伟蓉. STAT3/Th17细胞与干燥综合征的研究进展[J]. 中国药科大学学报, 2024, 55(3): 420-428. |
| [40] | Wu, H., Ivanov, I.I., Darce, J., Hattori, K., Shima, T., Umesaki, Y., et al. (2010) Gut-Residing Segmented Filamentous Bacteria Drive Autoimmune Arthritis via T Helper 17 Cells. Immunity, 32, 815-827. https://doi.org/10.1016/j.immuni.2010.06.001 |
| [41] | Zhuang, Y., Shi, Y., Liu, X., Zhang, J., Liu, T., Fan, X., et al. (2011) Helicobacter pylori-Infected Macrophages Induce Th17 Cell Differentiation. Immunobiology, 216, 200-207. https://doi.org/10.1016/j.imbio.2010.05.005 |
| [42] | Codolo, G., Amedei, A., Steere, A.C., Papinutto, E., Cappon, A., Polenghi, A., et al. (2008) Borrelia burgdorferi Napa-Driven Th17 Cell Inflammation in Lyme Arthritis. Arthritis & Rheumatism, 58, 3609-3617. https://doi.org/10.1002/art.23972 |
| [43] | Ma, X., Gao, Y., Chen, Y., Liu, J., Yang, C., Bao, C., et al. (2021) M2-Type Macrophages Induce Tregs Generation by Activating the TGF-β/SMAD Signalling Pathway to Promote Colorectal Cancer Development. OncoTargets and Therapy, 14, 5391-5402. https://doi.org/10.2147/ott.s336548 |
| [44] | Sun, H., Lee, H., Kim, S.H., Fernandes de Lima, M., Gingras, A.R., Du, Q., et al. (2023) IL-2 Can Signal via Chemokine Receptors to Promote Regulatory T Cells’ Suppressive Function. Cell Reports, 42, Article ID: 112996. https://doi.org/10.1016/j.celrep.2023.112996 |
| [45] | Liu, X., Zhang, W., Han, Y., Cheng, H., Liu, Q., Ke, S., et al. (2024) FOXP3+ Regulatory T Cell Perturbation Mediated by the IFNγ-STAT1-IFITM3 Feedback Loop Is Essential for Anti-Tumor Immunity. Nature Communications, 15, Article No. 122. https://doi.org/10.1038/s41467-023-44391-9 |
| [46] | Liu, Y., Wang, L., Predina, J., Han, R., Beier, U.H., Wang, L.S., et al. (2013) Inhibition of p300 Impairs Foxp3+ T Regulatory Cell Function and Promotes Antitumor Immunity. Nature Medicine, 19, 1173-1177. https://doi.org/10.1038/nm.3286 |
| [47] | Li, Y., Lu, Y., Lin, S., Li, N., Han, Y., Huang, Q., et al. (2021) Insulin Signaling Establishes a Developmental Trajectory of Adipose Regulatory T Cells. Nature Immunology, 22, 1175-1185. https://doi.org/10.1038/s41590-021-01010-3 |
| [48] | Arroyo‐Jousse, V., Borzutzky, A., Bono, M.R. and Casanello, P. (2023) Maternal Obesity Is Associated with a Higher Number of Regulatory‐T‐Cells in Newborns without Affecting Suppression. American Journal of Reproductive Immunology, 89, e13687. https://doi.org/10.1111/aji.13687 |
| [49] | Takahashi, D., Hoshina, N., Kabumoto, Y., Maeda, Y., Suzuki, A., Tanabe, H., et al. (2020) Microbiota-Derived Butyrate Limits the Autoimmune Response by Promoting the Differentiation of Follicular Regulatory T Cells. eBioMedicine, 58, Article ID: 102913. https://doi.org/10.1016/j.ebiom.2020.102913 |
| [50] | Du, H., Yue, S., Niu, D., Liu, C., Zhang, L., Chen, J., et al. (2022) Gut Microflora Modulates Th17/Treg Cell Differentiation in Experimental Autoimmune Prostatitis via the Short-Chain Fatty Acid Propionate. Frontiers in Immunology, 13, Article 915218. https://doi.org/10.3389/fimmu.2022.915218 |
| [51] | Yang, X.O., Nurieva, R., Martinez, G.J., Kang, H.S., Chung, Y., Pappu, B.P., et al. (2008) Molecular Antagonism and Plasticity of Regulatory and Inflammatory T Cell Programs. Immunity, 29, 44-56. https://doi.org/10.1016/j.immuni.2008.05.007 |
| [52] | Lee, G.R. (2018) The Balance of Th17 versus Treg Cells in Autoimmunity. International Journal of Molecular Sciences, 19, Article 730. https://doi.org/10.3390/ijms19030730 |
| [53] | Zhang, X., Zhang, X., Qiu, C., Shen, H., Zhang, H., He, Z., et al. (2021) The Imbalance of Th17/Treg via STAT3 Activation Modulates Cognitive Impairment in P. gingivalis LPS-Induced Periodontitis Mice. Journal of Leukocyte Biology, 110, 511-524. https://doi.org/10.1002/jlb.3ma0521-742rrr |
| [54] | Hajimoradi, M., Rezalotfi, A., Esmaeilnejad-Ahranjani, P., Mohammad Hassan, Z. and Ebrahimi, M. (2022) STAT3 Inactivation Suppresses Stemness Properties in Gastric Cancer Stem Cells and Promotes Th17 in Treg/Th17 Balance. International Immunopharmacology, 111, Article ID: 109048. https://doi.org/10.1016/j.intimp.2022.109048 |
| [55] | Korn, T., Mitsdoerffer, M., Croxford, A.L., Awasthi, A., Dardalhon, V.A., Galileos, G., et al. (2008) IL-6 Controls Th17 Immunity in Vivo by Inhibiting the Conversion of Conventional T Cells into Foxp3+ Regulatory T Cells. Proceedings of the National Academy of Sciences of the United States of America, 105, 18460-18465. https://doi.org/10.1073/pnas.0809850105 |
| [56] | 闫虎儿, 雒靖莎, 闫欢欢. Th17与Treg平衡的研究进展[J]. 新疆医学, 2024, 54(7): 847-852. |
| [57] | Mu, P., Huo, J., Li, X., Li, W., Li, X., Ao, J., et al. (2022) IL-2 Signaling Couples the MAPK and mTORC1 Axes to Promote T Cell Proliferation and Differentiation in Teleosts. The Journal of Immunology, 208, 1616-1631. https://doi.org/10.4049/jimmunol.2100764 |
| [58] | Wu, C., Yosef, N., Thalhamer, T., Zhu, C., Xiao, S., Kishi, Y., et al. (2013) Induction of Pathogenic TH17 Cells by Inducible Salt-Sensing Kinase SGK1. Nature, 496, 513-517. https://doi.org/10.1038/nature11984 |
| [59] | Côrte-Real, B.F., Hamad, I., Arroyo Hornero, R., Geisberger, S., Roels, J., Van Zeebroeck, L., et al. (2023) Sodium Perturbs Mitochondrial Respiration and Induces Dysfunctional Tregs. Cell Metabolism, 35, 299-315.e8. https://doi.org/10.1016/j.cmet.2023.01.009 |
| [60] | Hsu, T. and Lai, M. (2018) Hypoxia-Inducible Factor 1α Plays a Predominantly Negative Role in Regulatory T Cell Functions. Journal of Leukocyte Biology, 104, 911-918. https://doi.org/10.1002/jlb.mr1217-481r |
| [61] | Wilson, A.S., Randall, K.L., Pettitt, J.A., Ellyard, J.I., Blumenthal, A., Enders, A., et al. (2022) Neutrophil Extracellular Traps and Their Histones Promote Th17 Cell Differentiation Directly via TLR2. Nature Communications, 13, Article No. 528. https://doi.org/10.1038/s41467-022-28172-4 |
| [62] | Huijskens, M.J.A.J., Walczak, M., Sarkar, S., Atrafi, F., Senden-Gijsbers, B.L.M.G., Tilanus, M.G.J., et al. (2015) Ascorbic Acid Promotes Proliferation of Natural Killer Cell Populations in Culture Systems Applicable for Natural Killer Cell Therapy. Cytotherapy, 17, 613-620. https://doi.org/10.1016/j.jcyt.2015.01.004 |
| [63] | Zhao, N., Liu, C., Zhu, C., Dong, X. and Liu, X. (2019) Pidotimod: A Review of Its Pharmacological Features and Clinical Effectiveness in Respiratory Tract Infections. Expert Review of Anti-Infective Therapy, 17, 803-818. https://doi.org/10.1080/14787210.2019.1679118 |
