网络出版日期: 2021-08-09
基金资助
上海市自然科学基金(20ZR1448400)
Research progress in the mechanism of helper T cell 17 and regulatory T cell in depression
Online published: 2021-08-09
Supported by
Natural Science Foundation of Shanghai(20ZR1448400)
抑郁症是一种全球性的精神疾病，发病率逐年上升，疾病负担重且发病机制复杂。近年来，随着对抑郁症炎症假说研究的不断深入，学者们发现该疾病的发生发展与辅助性T细胞17（helper T cell 17，Th17）和调节性T细胞（regulatory T cell，Treg）介导的免疫失衡密切关联。而且，有关报道指出Th17和Treg均可受肠道菌群的调节，而肠道菌群可通过脑-肠轴机制参与抑郁症的发病过程。此外，在基础实验研究和临床治疗中发现，外周血中Th17和Treg的水平能够影响抗抑郁药的疗效。因此，该文结合肠道菌群的研究，对Th17和Treg在抑郁症发病机制和抗抑郁药治疗中作用的研究进展进行简要综述。
袁瑞雪 , 傅迎美 , 禹顺英 . 辅助性T细胞17和调节性T细胞在抑郁症中的作用机制研究进展[J]. 上海交通大学学报（医学版）, 2021 , 41(10) : 1384 -1388 . DOI: 10.3969/j.issn.1674-8115.2021.10.018
Depression is a global mental illness with increasing incidence, heavy disease burden and complicated pathogenesis. In recent years, based on the inflammatory hypothesis of depression, studies have demonstrated that the occurrence and development of the disease is closely related to the immune imbalance mediated by helper T cell 17 (Th17) and regulatory T cell (Treg). Moreover, reports have shown that both Th17 and Treg can be regulated by gut microbiome which involves in the pathogenesis of depression through the brain-gut axis mechanism. In addition, basic and clinical researches reveal that the levels of Th17 and Treg in peripheral blood are capable of affecting the efficacy of antidepressants. Therefore, this article combines the studies of gut microbiome to briefly review the research progress in the effect of Th17 and Treg on the pathogenesis of depression and the treatment of antidepressants.
| 1 | Huang Y, Wang Y, Wang H, et al. Prevalence of mental disorders in China: a cross-sectional epidemiological study[J]. Lancet Psychiatry, 2019, 6(3): 211-224. |
| 2 | Ma YJ, Zhou YJ, Wang DF, et al. Association of lipid profile and suicide attempts in a large sample of first episode drug-naive patients with major depressive disorder[J]. Front Psychiatry, 2020, 11: 543632. |
| 3 | 卢静茹, 张迎黎, 陈冠婕, 等. 抑郁障碍伴自杀风险的炎症机制相关研究进展[J]. 国际精神病学杂志, 2019, 46(6): 964-967. |
| 4 | Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report[J]. Am J Psychiatry, 2006, 163(11): 1905-1917. |
| 5 | Jacob L, Rockel T, Kostev K. Depression risk in patients with rheumatoid arthritis in the United Kingdom[J]. Rheumatol Ther, 2017, 4(1): 195-200. |
| 6 | Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis[J]. Psychosom Med, 2009, 71(2): 171-186. |
| 7 | Liu Y, Ho RC, Mak A. Interleukin (IL)-6, tumour necrosis factor α (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression[J]. J Affect Disord, 2012, 139(3): 230-239. |
| 8 | Ellul P, Mariotti-Ferrandiz E, Leboyer M, et al. Regulatory T cells as supporters of psychoimmune resilience: toward immunotherapy of major depressive disorder[J]. Front Neurol, 2018, 9: 167. |
| 9 | Moaaz M, Youssry S, Elfatatry A, et al. Th17/Treg cells imbalance and their related cytokines (IL-17, IL-10 and TGF-β) in children with autism spectrum disorder[J]. J Neuroimmunol, 2019, 337: 577071. |
| 10 | 顾娜, 刘洪斌. Th17/Treg免疫失衡在肺部疾病中的研究进展[J].天津药学, 2019, 31(2): 58-62. |
| 11 | 褚璨灿, 师为人, 陈云志, 等. 基于Th17/Treg细胞平衡探讨调节肠道菌群与防治COPD的相关研究[J]. 湖北民族学院学报(医学版), 2019, 36(3): 61-63. |
| 12 | Ivanov II, McKenzie BS, Zhou L, et al. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells[J]. Cell, 2006, 126(6): 1121-1133. |
| 13 | Lee GR. The balance of Th17 versus Treg cells in autoimmunity[J]. Int J Mol Sci, 2018, 19(3): 730. |
| 14 | Yang L, Anderson DE, Baecher-Allan C, et al. IL-21 and TGF-β are required for differentiation of human T(H)17 cells[J]. Nature, 2008, 454(7202): 350-352. |
| 15 | Kleinewietfeld M, Hafler DA. The plasticity of human Treg and Th17 cells and its role in autoimmunity[J]. Semin Immunol, 2013, 25(4): 305-312. |
| 16 | Muranski P, Restifo NP. Essentials of Th17 cell commitment and plasticity[J]. Blood, 2013, 121(13): 2402-2414. |
| 17 | Fasching P, Stradner M, Graninger W, et al. Therapeutic potential of targeting the Th17/Treg axis in autoimmune disorders[J]. Molecules, 2017, 22(1): 134. |
| 18 | Beurel E, Harrington LE, Jope RS. Inflammatory T helper 17 cells promote depression-like behavior in mice[J]. Biol Psychiatry, 2013, 73(7): 622-630. |
| 19 | Beurel E, Lowell JA, Jope RS. Distinct characteristics of hippocampal pathogenic TH17 cells in a mouse model of depression[J]. Brain Behav Immun, 2018, 73: 180-191. |
| 20 | Beurel E, Lowell JA. Th17 cells in depression[J]. Brain Behav Immun, 2018, 69: 28-34. |
| 21 | Chen Y, Jiang T, Chen P, et al. Emerging tendency towards autoimmune process in major depressive patients: a novel insight from Th17 cells[J]. Psychiatry Res, 2011, 188(2): 224-230. |
| 22 | Schiweck C, Valles-Colomer M, Arolt V, et al. Depression and suicidality: a link to premature T helper cell aging and increased Th17 cells[J]. Brain Behav Immun, 2020, 87: 603-609. |
| 23 | Ghosh R, Kumar PK, Mitra P, et al. Circulating T helper 17 and IFN-γ positive Th17 cells in major depressive disorder[J]. Behav Brain Res, 2020, 394: 112811. |
| 24 | Slyepchenko A, Maes M, K?hler CA, et al. T helper 17 cells may drive neuroprogression in major depressive disorder: proposal of an integrative model[J]. Neurosci Biobehav Rev, 2016, 64: 83-100. |
| 25 | Ang QY, Alexander M, Newman JC, et al. Ketogenic diets alter the gut microbiome resulting in decreased intestinal Th17 cells[J]. Cell, 2020, 181(6): 1263-1275. |
| 26 | Medina-Rodriguez EM, Madorma D, O'Connor G, et al. Identification of a signaling mechanism by which the microbiome regulates Th17 cell-mediated depressive-like behaviors in mice[J]. Am J Psychiatry, 2020, 177(10): 974-990. |
| 27 | Li J, Zhao R, Li X, et al. Shen-Qi-Jie-Yu-Fang exerts effects on a rat model of postpartum depression by regulating inflammatory cytokines and CD4+ CD25+ regulatory T cells[J]. Neuropsychiatr Dis Treat, 2016, 12: 883-896. |
| 28 | Li Y, Xiao B, Qiu W, et al. Altered expression of CD4+ CD25+ regulatory T cells and its 5-HT(1a) receptor in patients with major depression disorder[J]. J Affect Disord, 2010, 124(1/2): 68-75. |
| 29 | Zhou L, Chu C, Teng F, et al. Innate lymphoid cells support regulatory T cells in the intestine through interleukin-2[J]. Nature, 2019, 568(7752): 405-409. |
| 30 | Lee N, Kim WU. Microbiota in T-cell homeostasis and inflammatory diseases[J]. Exp Mol Med, 2017, 49(5): e340. |
| 31 | Cheng H, Guan X, Chen D, et al. The Th17/Treg cell balance: a gut microbiota-modulated story[J]. Microorganisms, 2019, 7(12): 583. |
| 32 | Atarashi K, Tanoue T, Oshima K, et al. Treg induction by a rationally selected mixture of clostridia strains from the human microbiota[J]. Nature, 2013, 500(7461): 232-236. |
| 33 | Narushima S, Sugiura Y, Oshima K, et al. Characterization of the 17 strains of regulatory T cell-inducing human-derived clostridia[J]. Gut Microbes, 2014, 5(3): 333-339. |
| 34 | Westfall S, Caracci F, Zhao D, et al. Microbiota metabolites modulate the T helper 17 to regulatory T cell (Th17/Treg) imbalance promoting resilience to stress-induced anxiety- and depressive-like behaviors[J]. Brain Behav Immun, 2021, 91: 350-368. |
| 35 | 刘姝, 王飞. 溃疡性结肠炎患者肠道菌群紊乱与Th17/Treg及其分泌炎性细胞因子免疫平衡的关系[J]. 现代医学, 2020, 48(7): 862-867. |
| 36 | Vojvodic J, Mihajlovic G, Vojvodic P, et al. The impact of immunological factors on depression treatment - relation between antidepressants and immunomodulation agents[J]. Open Access Maced J Med Sci, 2019, 7(18): 3064-3069. |
| 37 | Jha MK, Minhajuddin A, Gadad BS, et al. Interleukin 17 selectively predicts better outcomes with bupropion-SSRI combination: novel T cell biomarker for antidepressant medication selection[J]. Brain Behav Immun, 2017, 66: 103-110. |
| 38 | Zhang Y, Zhen H, Yao W, et al. Antidepressant drug, desipramine, alleviates allergic rhinitis by regulating Treg and Th17 cells[J]. Int J Immunopathol Pharmacol, 2013, 26(1): 107-115. |
| 39 | Mohd Ashari NS, Mohamed Sanusi SNF, Mohd Yasin MA, et al. Major depressive disorder patients on antidepressant treatments display higher number of regulatory T cells[J]. Malays J Pathol, 2019, 41(2): 169-176. |
| 40 | Woelfer M, Kasties V, Kahlfuss S, et al. The role of depressive subtypes within the neuroinflammation hypothesis of major depressive disorder[J]. Neuroscience, 2019, 403: 93-110. |
| 41 | Grosse L, Carvalho LA, Birkenhager TK, et al. Circulating cytotoxic T cells and natural killer cells as potential predictors for antidepressant response in melancholic depression. Restoration of T regulatory cell populations after antidepressant therapy[J]. Psychopharmacology (Berl), 2016, 233(9): 1679-1688. |
/
| 〈 |
|
〉 |