Interleukin-2 expands neuroprotective regulatory T cells in Parkinson's disease.
| Autor: | Markovic M; Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders, University of Nebraska Medical Center, 68198 Omaha, NE, USA., Yeapuri P; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA., Namminga KL; Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders, University of Nebraska Medical Center, 68198 Omaha, NE, USA., Lu Y; Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders, University of Nebraska Medical Center, 68198 Omaha, NE, USA., Saleh M; Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders, University of Nebraska Medical Center, 68198 Omaha, NE, USA., Olson KE; Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders, University of Nebraska Medical Center, 68198 Omaha, NE, USA., Gendelman HE; Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders, University of Nebraska Medical Center, 68198 Omaha, NE, USA., Mosley RL; Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders, University of Nebraska Medical Center, 68198 Omaha, NE, USA. |
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| Jazyk: | angličtina |
| Zdroj: | NeuroImmune pharmacology and therapeutics [NeuroImmune Pharm Ther] 2022 Jun 21; Vol. 1 (1), pp. 43-50. Date of Electronic Publication: 2022 Jun 21 (Print Publication: 2022). |
| DOI: | 10.1515/nipt-2022-0001 |
| Abstrakt: | 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 × 10 4 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 6 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 + CD127 low FoxP3 + 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. Competing Interests: Competing interests: Authors state no conflict of interest. (© 2022 the author(s), published by De Gruyter, Berlin/Boston.) |
| Databáze: | MEDLINE |
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