Journal
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
Volume 15, Issue 2, Pages 224-237Publisher
SPRINGER
DOI: 10.1007/s11481-019-09888-5
Keywords
Regulatory T cells; Parkinson's disease; Dopaminergic neurons; CD45; Galectin-1
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Funding
- National Natural Science Foundation of China [31771293, 81701633]
- Nantong University [18B13]
- Natural Science Foundation of Jiangsu Province of China - Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions [BK20180948]
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Regulatory T cells (Tregs), which secrete transforming growth factor (TGF)-beta and interleukin (IL)-10, have essential role in anti-inflammatory and neurotrophic functions. Herein, we explore the neuroprotection of Tregs in Parkinson's disease (PD) by adoptive transfer of Tregs. Tregs, isolated by magnetic sorting, were activated in vitro and then were adoptively transferred to 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-treated mice. Neuroinflammation, dopaminergic neuronal loss and behavioral changes of PD mice were evaluated. Live cell imaging system detected a dynamic contact of Tregs with MN9D cells that were stained with CD45 and galectin-1, respectively. Tregs prevented MPTP-induced dopaminergic neuronal loss, behavioral changes, and attenuated the inflammatory reaction in the brain. When blockade the LFA-1 activity in Tregs or the ICAM-1 activity in endothelial cells, the percentage of Tregs in substantia nigra (SN) decreased. CD45 and galectin-1 were expressed by Tregs and MN9D cells, respectively. CD45-labeled Tregs dynamically contacted with galectin-1-labeled MN9D cells. Inhibiting CD45 in Tregs impaired the ability of Tregs to protect dopaminergic neurons against MPP+ toxicity. Similarly, galectin-1 knockdown in MN9D cells reduced the ability of Tregs neuroprotection. Adoptive transfer of Tregs protects dopaminergic neurons in PD mice by a cell-to-cell contact mechanism underlying CD45-galectin-1 interaction.
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