Роль Т-клеточных субпопуляций в патогенезе и терапии болезни Паркинсона (обзор литературы)

Роль Т-клеточных субпопуляций в патогенезе и терапии болезни Паркинсона (обзор литературы)

 

Авторы

 

Г.В. Идова

ФГБНУ «Научно-исследовательский институт нейронаук и медицины», Новосибирск, Россия

Е.Л. Альперина

ФГБНУ «Научно-исследовательский институт нейронаук и медицины», Новосибирск, Россия

С.Я. Жанаева

ФГБНУ «Научно-исследовательский институт нейронаук и медицины», Новосибирск, Россия

 

https://doi.org/10.26617/1810-3111-2023-1(118)-96-103

 

Журнал:Сибирский вестник психиатрии и наркологии. 2023; 1(118): 96-103.

 

Реферат

Обзор литературы посвящен ключевой роли Т-лимфоцитов в патогенезе болезни Паркинсона (БП), изменение количества и функции которых на периферии и в головном мозге приводит к глубокому дисбалансу иммунной системы при развитии заболевания. Рассматриваются экспериментальные и клинические данные об участии провоспалительных (Тh1 и Th17) и противовоспалительных (Тh2 и Т-reg) иммунных клеток в процессе нейровоспаления и дегенерации дофаминовых нейронов. Приводятся данные о возможности использования оценки периферических Т-клеток в качестве диагностических и терапевтических биомаркеров. Обсуждаются способы модуляции Т-клеточного ответа как эффективной стратегии нейропротекции.

 

Ключевые слова: болезнь Паркинсона, нейровоспаление, нейродегенерация, субпопуляции Т-клеток, инфильтрация мозга, терапия.

 

Статья (pdf)

 

Связь с автором

Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра.

 

Дополнительные материалы

 

Для цитирования: Идова Г.В., Альперина Е.Л., Жанаева С.Я. Роль Т-клеточных субпопуляций в патогенезе и терапии болезни Паркинсона (обзор литературы). Сибирский вестник психиатрии и наркологии. 2023. № 1 (118). С. 96-103. https://doi.org/10.26617/1810-3111-2023-1(118)-96-103

 

Литература

  1. Kalia LV, Lang AE. Parkinson’s disease. Lancet. 2015;386:896–912.doi: 10.1016/S0140-6736(14)61393-3.
  2. Dickson DW. Neuropathology of Parkinson disease. Parkinsonism Relat Disord. 2018 Jan;46 Suppl 1(Suppl 1):S30-S33. doi: 10.1016/j.parkreldis. 2017.07.033. Epub 2017 Aug 1. PMID: 28780180; PMCID: PMC5718208.
  3. Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol. 2020 Jan;27(1):27-42. doi: 10.1111/ene. 14108. Epub 2019 Nov 27. PMID: 31631455.
  4. Ugrumov M. Development of early diagnosis of Parkinson's disease: Illusion or reality? CNS Neurosci Ther. 2020 Oct;26(10):997-1009. doi: 10.1111/cns.13429. Epub 2020 Jun 29. PMID: 32597012; PMCID: PMC7539842.
  5. Tan EK, Chao YX, West A, Chan LL, Poewe W, Jankovic J. Parkinson disease and the immune system ‒ associations, mechanisms and therapeutics. Nat Rev Neurol. 2020 Jun;16(6):303-318. doi: 10.1038/s41582-020-0344-4. Epub 2020 Apr 24. PMID: 32332985.
  6. Williams GP, Schonhoff AM, Jurkuvenaite A, Gallups NJ, Standaert DG, Harms AS. CD4 T cells mediate brain inflammation and neurodegeneration in a mouse model of Parkinson's disease. Brain. 2021 Aug 17;144(7):2047-2059. doi: 10.1093/brain/awab103. PMID:33704423; PMCID: PMC8370411.
  7. Weiss F, Labrador-Garrido A, Dzamko N, Halliday G. Immune responses in the Parkinson's disease brain. Neurobiol Dis. 2022 Jun 15;168:105700. doi: 10.1016/j.nbd.2022.105700. Epub 2022 Mar 18. PMID: 35314321.
  8. Wang T, Shi C, Luo H, Zheng H, Fan L, Tang M, Su Y, Yang J, Mao C, Xu Y. Neuroinflammation in Parkinson's Disease: Triggers, Mechanisms, and Immunotherapies. Neuroscientist. 2022 Aug;28(4):364-381. doi: 10.1177/1073858421991066. Epub 2021 Feb 12. PMID: 33576313.
  9. Xu Y, Li Y, Wang C, Han T, Liu H, Sun L, Hong J, Hashimoto M, Wei J. The reciprocal interactions between microglia and T cells in Parkinson's disease: a double-edged sword. J Neuroinflammation. 2023 Feb 12;20(1):33. doi: 10.1186/s12974-023-02723-y. PMID: 36774485; PMCID: PMC9922470.
  10. Baird JK, Bourdette D, Meshul CK, Quinn JF. The key role of T cells in Parkinson's disease pathogenesis and therapy. Parkinsonism Relat Disord. 2019 Mar;60:25-31. doi: 10.1016/j.parkreldis. 2018.10.029. Epub 2018 Oct 28. PMID: 30404763.
  11. Chen Z, Chen S, Liu J. The role of T cells in the pathogenesis of Parkinson's disease. Prog Neurobiol. 2018 Oct;169:1-23. doi: 10.1016/j.pneurobio.2018.08.002. Epub 2018 Aug 13. PMID: 30114440.
  12. MacMahon Copas AN, McComish SF, Fletcher JM, Caldwell MA. The pathogenesis of Parkinson's disease: a complex interplay between astrocytes, microglia, and t lymphocytes? Front Neurol. 2021 May 26;12:666737. doi: 10.3389/fneur.2021.666737. PMID: 34122308; PMCID: PMC8189423.
  13. Brochard V, Combadière B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, Bonduelle O, Alvarez-Fischer D, Callebert J, Launay JM, Duyckaerts C, Flavell RA, Hirsch EC, Hunot S. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest. 2009 Jan;119(1):182-92. doi: 10.1172/JCI36470. Epub 2008 Dec 22. PMID: 19104149; PMCID: PMC2613467.
  14. Sommer A, Fadler T, Dorfmeister E, Hoffmann AC, Xiang W, Winner B, Prots I. Infiltrating T lymphocytes reduce myeloid phagocytosis activity in synucleinopathy model. J Neuroinflammation. 2016 Jun 30;13(1):174. doi: 10.1186/s12974-016-0632-5. PMID: 27364890; PMCID: PMC4929755.
  15. Contaldi E, Magistrelli L, Comi C. T Lymphocytes in Parkinson's Disease. J Parkinsons Dis. 2022;12(s1):S65-S74. doi: 10.3233/JPD-223152. PMID: 35253782; PMCID: PMC9535550.
  16. González H, Contreras F, Prado C, Elgueta D, Franz D, Bernales S, Pacheco R. Dopamine receptor D3 expressed on CD4+ T cells favors neurodegeneration of dopaminergic neurons during Parkinson's disease. J Immunol. 2013 May 15;190(10):5048-56. doi: 10.4049/jimmunol.1203121. Epub 2013 Apr 15. PMID: 23589621.
  17. González H, Contreras F, Pacheco R. Regulation of the Neurodegenerative Process Associated to Parkinson's Disease by CD4+ T-cells. J Neuroimmune Pharmacol. 2015 Dec;10(4):561-75. doi: 10.1007/s11481-015-9618-9. Epub 2015 May 28. PMID: 26018603.
  18. Harms AS, Ferreira SA, Romero-Ramos M. Periphery and brain, innate and adaptive immunity in Parkinson's disease. Acta Neuropathol. 2021 Apr;141(4):527-545. doi: 10.1007/s00401-021-02268-5. Epub 2021 Feb 8. PMID: 33555429; PMCID: PMC7952334.
  19. Sulzer D, Alcalay RN, Garretti F, Cote L, Kanter E, Agin-Liebes J, Liong C, McMurtrey C, Hildebrand WH, Mao X, Dawson VL, Dawson TM, Oseroff C, Pham J, Sidney J, Dillon MB, Carpenter C, Weiskopf D, Phillips E, Mallal S, Peters B, Frazier A, Lindestam Arlehamn CS, Sette A. T cells from patients with Parkinson's disease recognize α-synuclein peptides. Nature. 2017 Jun 29;546(7660): 656-661. doi: 10.1038/nature22815. Epub 2017 Jun 21. Erratum in: Nature. 2017 Sep 13;549(7671):292. PMID: 28636593; PMCID: PMC5626019.
  20. Sommer A, Marxreiter F, Krach F, Fadler T, Grosch J, Maroni M, Graef D, Eberhardt E, Riemenschneider MJ, Yeo GW, Kohl Z, Xiang W, Gage FH, Winkler J, Prots I, Winner B. Th17 lymphocytes induce neuronal cell death in a human ipsc-based model of Parkinson's disease. Cell Stem Cell. 2018 Jul 5;23(1):123-131.e6. doi: 10.1016/j.stem.2018.06.015. Erratum in: Cell Stem Cell. 2019 Jun 6;24(6):1006. PMID: 29979986.
  21. Garretti F, Monahan C, Sette A, Agalliu D, Sulzer D. T cells, α-synuclein and Parkinson disease. Handb Clin Neurol. 2022;184:439-455. doi: 10.1016/B978-0-12-819410-2.00023-0. PMID: 35034753.
  22. Lindestam Arlehamn CS, Dhanwani R, Pham J, Kuan R, Frazier A, Rezende Dutra J, Phillips E, Mallal S, Roederer M, Marder KS, Amara AW, Standaert DG, Goldman JG, Litvan I, Peters B, Sulzer D, Sette A. α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson's disease. Nat Commun. 2020 Apr 20;11(1):1875. doi: 10.1038/s41467-020-15626-w. PMID: 32313102; PMCID: PMC7171193.
  23. Subbarayan MS, Hudson C, Moss LD, Nash KR, Bickford PC. T cell infiltration and upregulation of MHCII in microglia leads to accelerated neuronal loss in an α-synuclein rat model of Parkinson's disease. J Neuroinflammation. 2020 Aug 15;17(1):242. doi: 10.1186/s12974-020-01911-4. PMID: 32799878; PMCID: PMC7429710.
  24. Cen L, Yang C, Huang S, Zhou M, Tang X, Li K, Guo W, Wu Z, Mo M, Xiao Y, Chen X, Yang X, Huang Q, Chen C, Qu S, Xu P. Peripheral lymphocyte subsets as a marker of Parkinson's disease in a Chinese population. Neurosci Bull. 2017 Oct;33(5):493-500. doi: 10.1007/s12264-017-0163-9. Epub 2017 Aug 8. PMID: 28791571; PMCID: PMC5636734.
  25. Kustrimovic N, Comi C, Magistrelli L, Rasini E, Legnaro M, Bombelli R, Aleksic I, Blandini F, Minafra B, Riboldazzi G, Sturchio A, Mauri M, Bono G, Marino F, Cosentino M. Parkinson's disease patients have a complex phenotypic and functional Th1 bias: cross-sectional studies of CD4+ Th1/Th2/T17 and Treg in drug-naïve and drug-treated patients. J Neuroinflammation. 2018 Jul 12;15(1):205. doi: 10.1186/s12974-018-1248-8. PMID: 30001736; PMCID: PMC6044047.
  26. Sun C, Zhao Z, Yu W, Mo M, Song C, Si Y, Liu Y. Abnormal subpopulations of peripheral blood lymphocytes are involved in Parkinson's disease. Ann Transl Med. 2019 Nov;7(22):637. doi: 10.21037/atm.2019.10.105. PMID: 31930038; PMCID: PMC6944630.
  27. Yan Z, Yang W, Wei H, Dean MN, Standaert DG, Cutter GR, Benveniste EN, Qin H. Dysregulation of the adaptive immune system in patients with early-stage Parkinson disease. Neurol Neuroimmunol Neuroinflamm. 2021 Jul 22;8(5):e1036. doi: 10.1212/NXI.0000000000001036. PMID: 34301818; PMCID: PMC8299515.
  28. Idova GV, Al'perina EL, Gevorgyan MM, Tikhonova MA, Zhanaeva SY. Content of peripheral blood T- and B-cell subpopulations in transgenic A53T mice of different age (a model of Parkinson's disease). Bull Exp Biol Med. 2021 Feb;170(4):401-404. doi: 10.1007/s10517-021-05075-w. PMID: 33725243.
  29. Garfias S, Tamaya Domínguez B, Toledo Rojas A, Arroyo M, Rodríguez U, Boll C, Sosa AL, Sciutto E, Adalid-Peralta L, Martinez López Y, Fragoso G, Fleury A. Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases. Neurologia (Engl Ed). 2022 Mar;37(2):110-121. doi: 10.1016/j.nrleng.2018.10.022. PMID: 35279225.
  30. Iba M, Kim C, Sallin M, Kwon S, Verma A, Overk C, Rissman RA, Sen R, Sen JM, Masliah E. Neuroinflammation is associated with infiltration of T cells in Lewy body disease and α-synuclein transgenic models. J Neuroinflammation. 2020 Jul 17;17(1):214. doi: 10.1186/s12974-020-01888-0. PMID: 32680537; PMCID: PMC7368752.
  31. Lai TT, Kim YJ, Ma HI, Kim YE. Evidence of Inflammation in Parkinson's Disease and Its Contribution to Synucleinopathy. J Mov Disord. 2022 Jan;15(1):1-14. doi: 10.14802/jmd.21078. PMID: 35124957; PMCID: PMC8820875.
  32. Wang P, Yao L, Luo M, Zhou W, Jin X, Xu Z, Yan S, Li Y, Xu C, Cheng R, Huang Y, Lin X, Ma K, Cao H, Liu H, Xue G, Han F, Nie H, Jiang Q. Single-cell transcriptome and TCR profiling reveal activated and expanded T cell populations in Parkinson's disease. Cell Discov. 2021 Jul 20;7(1):52. doi: 10.1038/s41421-021-00280-3. PMID: 34282123; PMCID: PMC8289849.
  33. Galiano-Landeira J, Torra A, Vila M, Bové J. CD8 T cell nigral infiltration precedes synucleinopathy in early stages of Parkinson's disease. Brain. 2020 Dec 1;143(12):3717-3733. doi: 10.1093/brain/awaa269. PMID: 33118032.
  34. Williams GP, Schonhoff AM, Jurkuvenaite A, Thome AD, Standaert DG, Harms AS. Targeting of the class II transactivator attenuates inflammation and neurodegeneration in an alpha-synuclein model of Parkinson's disease. J Neuroinflammation. 2018 Aug 30;15(1):244. doi: 10.1186/s12974-018-1286-2. PMID: 30165873; PMCID: PMC6117927.
  35. Appel SH. CD4+ T cells mediate cytotoxicity in neurodegenerative diseases. J Clin Invest. 2009 Jan;119(1):13-5. doi: 10.1172/JCI38096. PMID: 19104142; PMCID: PMC2613473.
  36. Rostami J, Fotaki G, Sirois J, Mzezewa R, Bergström J, Essand M, Healy L, Erlandsson A. Astrocytes have the capacity to act as antigen-presenting cells in the Parkinson's disease brain. J Neuroinflammation. 2020 Apr 16;17(1):119. doi: 10.1186/s12974-020-01776-7. PMID: 32299492; PMCID: PMC7164247.
  37. Chakrabarty P, Ceballos-Diaz C, Lin WL, Beccard A, Jansen-West K, McFarland NR, Janus C, Dickson D, Das P, Golde TE. Interferon-γ induces progressive nigrostriatal degeneration and basal ganglia calcification. Nat Neurosci. 2011 Jun;14(6):694-6. doi: 10.1038/nn.2829. Epub 2011 May 15. PMID: 21572432; PMCID: PMC3780582.
  38. Cebrián C, Zucca FA, Mauri P, Steinbeck JA, Studer L, Scherzer CR, Kanter E, Budhu S, Mandelbaum J, Vonsattel JP, Zecca L, Loike JD, Sulzer D. MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration. Nat Commun. 2014 Apr 16;5:3633. doi: 10.1038/ncomms4633. PMID: 24736453; PMCID: PMC4024461.
  39. Álvarez-Luquín DD, Arce-Sillas A, Leyva-Hernández J, Sevilla-Reyes E, Boll MC, Montes-Moratilla E, Vivas-Almazán V, Pérez-Correa C, Rodríguez-Ortiz U, Espinoza-Cárdenas R, Fragoso G, Sciutto E, Adalid-Peralta L. Regulatory impairment in untreated Parkinson's disease is not restricted to Tregs: other regulatory populations are also involved. J Neuroinflammation. 2019 Nov 11;16(1):212. doi: 10.1186/s12974-019-1606-1. PMID: 31711508; PMCID: PMC6849192.
  40. Chen X, Feng W, Ou R, Liu J, Yang J, Fu J, Cao B, Chen Y, Wei Q, Shang H. Evidence for Peripheral Immune Activation in Parkinson's Disease. Front Aging Neurosci. 2021 Apr 30;13:617370. doi: 10.3389/fnagi.2021.617370. PMID: 33994989; PMCID: PMC8119625.
  41. Chen J, Liu X, Zhong Y. Interleukin-17A: The Key Cytokine in Neurodegenerative Diseases. Front Aging Neurosci. 2020 Sep 29;12:566922. doi: 10.3389/fnagi.2020.566922. PMID: 33132897; PMCID: PMC7550684.
  42. Shi Y, Wei B, Li L, Wang B, Sun M. Th17 cells and inflammation in neurological disorders: Possible mechanisms of action. Front Immunol. 2022 Jul 22;13:932152. doi: 10.3389/fimmu.2022.932152. PMID: 35935951; PMCID: PMC9353135.
  43. Li J, Zhao J, Chen L, Gao H, Zhang J, Wang D, Zou Y, Qin Q, Qu Y, Li J, Xiong Y, Min Z, Yan M, Mao Z, Xue Z. α-Synuclein induces Th17 differentiation and impairs the function and stability of Tregs by promoting RORC transcription in Parkinson's disease. Brain Behav Immun. 2023 Feb;108:32-44. doi: 10.1016/j.bbi.2022.10.023. Epub 2022 Nov 4. PMID: 36343753.
  44. Joo J, Jeong J, Park HJ. Blood Biomarkers in Patients with Parkinson's Disease: A Review in Context of Anesthetic Care. Diagnostics (Basel). 2023 Feb 12;13(4):693. doi: 10.3390/diagnostics13040693. PMID: 36832181; PMCID: PMC9955162.
  45. Reynolds AD, Banerjee R, Liu J, Gendelman HE, Mosley RL. Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease. J Leukoc Biol. 2007 Nov;82(5):1083-94. doi: 10.1189/jlb.0507296. Epub 2007 Aug 3. PMID: 17675560.
  46. Fuzzati-Armentero MT, Cerri S, Blandini F. Peripheral-Central Neuroimmune Crosstalk in Parkinson's Disease: What Do Patients and Animal Models Tell Us? Front Neurol. 2019 Mar 19;10:232. doi: 10.3389/fneur.2019.00232. PMID: 30941089; PMCID: PMC6433876.
  47. Huang Y, Liu Z, Wang XQ, Qiu YH, Peng YP. A dysfunction of CD4+ T lymphocytes in peripheral immune system of Parkinson's disease model mice. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2014 Nov;30(6):567-76. PMID: 26016368.
  48. Schetters STT, Gomez-Nicola D, Garcia-Vallejo JJ, Van Kooyk Y. Neuroinflammation: Microglia and T Cells Get Ready to Tango. Front Immunol. 2018 Jan 25;8:1905. doi: 10.3389/fimmu.2017.01905. PMID: 29422891; PMCID: PMC5788906.
  49. Magistrelli L, Contaldi E, Comi C. The Immune System as a Therapeutic Target for Old and New Drugs in Parkinson's Disease. CNS Neurol Disord Drug Targets. 2023;22(1):66-70. doi: 10.2174/1871527321666220310122415. PMID: 35272601.
  50. Prots I, Winner B. Th17 cells: a promising therapeutic target for Parkinson's disease? Expert Opin Ther Targets. 2019 Apr;23(4):309-314. doi: 10.1080/14728222.2019.1590336. Epub 2019 Mar 14. PMID: 30871383.