Milica Markovic, Pravin Yeapuri, Krista L Namminga, Yaman Lu, Maamoon Saleh, Katherine E Olson, Howard E Gendelman, R Lee Mosley
{"title":"白细胞介素-2在帕金森病中扩展神经保护调节性T细胞","authors":"Milica Markovic, Pravin Yeapuri, Krista L Namminga, Yaman Lu, Maamoon Saleh, Katherine E Olson, Howard E Gendelman, R Lee Mosley","doi":"10.1515/nipt-2022-0001","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Pharmacological approaches that boost neuroprotective regulatory T cell (Treg) number and function lead to neuroprotective activities in neurodegenerative disorders.</p><p><strong>Objectives: </strong>We investigated whether low-dose interleukin 2 (IL-2) expands Treg populations and protects nigrostriatal dopaminergic neurons in a model of Parkinson's disease (PD).</p><p><strong>Methods: </strong>IL-2 at 2.5 × 10<sup>4</sup> IU/dose/mouse was administered for 5 days. Lymphocytes were isolated and phenotype determined by flow cytometric analyses. To 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice, 0.5 × 10<sup>6</sup> of enriched IL-2-induced Tregs were adoptively transferred to assess the effects on nigrostriatal neuron survival.</p><p><strong>Results: </strong>IL-2 increased frequencies of CD4<sup>+</sup>CD25<sup>+</sup>CD127<sup>low</sup>FoxP3<sup>+</sup> Tregs that express ICOS and CD39 in blood and spleen. Adoptive transfer of IL-2-induced Tregs to MPTP-treated recipients increased tyrosine hydroxylase (TH)<sup>+</sup> nigral dopaminergic neuronal bodies by 51% and TH<sup>+</sup> striatal termini by 52% compared to control MPTP-treated animal controls.</p><p><strong>Conclusions: </strong>IL-2 expands numbers of neuroprotective Tregs providing a vehicle for neuroprotection of nigrostriatal dopaminergic neurons in a pre-clinical PD model.</p>","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"1 1","pages":"43-50"},"PeriodicalIF":0.0000,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254387/pdf/","citationCount":"0","resultStr":"{\"title\":\"Interleukin-2 expands neuroprotective regulatory T cells in Parkinson's disease.\",\"authors\":\"Milica Markovic, Pravin Yeapuri, Krista L Namminga, Yaman Lu, Maamoon Saleh, Katherine E Olson, Howard E Gendelman, R Lee Mosley\",\"doi\":\"10.1515/nipt-2022-0001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Pharmacological approaches that boost neuroprotective regulatory T cell (Treg) number and function lead to neuroprotective activities in neurodegenerative disorders.</p><p><strong>Objectives: </strong>We investigated whether low-dose interleukin 2 (IL-2) expands Treg populations and protects nigrostriatal dopaminergic neurons in a model of Parkinson's disease (PD).</p><p><strong>Methods: </strong>IL-2 at 2.5 × 10<sup>4</sup> IU/dose/mouse was administered for 5 days. Lymphocytes were isolated and phenotype determined by flow cytometric analyses. To 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice, 0.5 × 10<sup>6</sup> of enriched IL-2-induced Tregs were adoptively transferred to assess the effects on nigrostriatal neuron survival.</p><p><strong>Results: </strong>IL-2 increased frequencies of CD4<sup>+</sup>CD25<sup>+</sup>CD127<sup>low</sup>FoxP3<sup>+</sup> Tregs that express ICOS and CD39 in blood and spleen. Adoptive transfer of IL-2-induced Tregs to MPTP-treated recipients increased tyrosine hydroxylase (TH)<sup>+</sup> nigral dopaminergic neuronal bodies by 51% and TH<sup>+</sup> striatal termini by 52% compared to control MPTP-treated animal controls.</p><p><strong>Conclusions: </strong>IL-2 expands numbers of neuroprotective Tregs providing a vehicle for neuroprotection of nigrostriatal dopaminergic neurons in a pre-clinical PD model.</p>\",\"PeriodicalId\":74278,\"journal\":{\"name\":\"NeuroImmune pharmacology and therapeutics\",\"volume\":\"1 1\",\"pages\":\"43-50\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-06-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254387/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"NeuroImmune pharmacology and therapeutics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1515/nipt-2022-0001\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/3/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"NeuroImmune pharmacology and therapeutics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1515/nipt-2022-0001","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/3/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
Interleukin-2 expands neuroprotective regulatory T cells in Parkinson's disease.
Background: Pharmacological approaches that boost neuroprotective regulatory T cell (Treg) number and function lead to neuroprotective activities in neurodegenerative disorders.
Objectives: We investigated whether low-dose interleukin 2 (IL-2) expands Treg populations and protects nigrostriatal dopaminergic neurons in a model of Parkinson's disease (PD).
Methods: IL-2 at 2.5 × 104 IU/dose/mouse was administered for 5 days. Lymphocytes were isolated and phenotype determined by flow cytometric analyses. To 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice, 0.5 × 106 of enriched IL-2-induced Tregs were adoptively transferred to assess the effects on nigrostriatal neuron survival.
Results: IL-2 increased frequencies of CD4+CD25+CD127lowFoxP3+ Tregs that express ICOS and CD39 in blood and spleen. Adoptive transfer of IL-2-induced Tregs to MPTP-treated recipients increased tyrosine hydroxylase (TH)+ nigral dopaminergic neuronal bodies by 51% and TH+ striatal termini by 52% compared to control MPTP-treated animal controls.
Conclusions: IL-2 expands numbers of neuroprotective Tregs providing a vehicle for neuroprotection of nigrostriatal dopaminergic neurons in a pre-clinical PD model.
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