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Bee Venom Phospholipase A2, a Novel Foxp3+ Regulatory T Cell Inducer, Protects Dopaminergic Neurons by Modulating Neuroinflammatory Responses in a Mouse Model of Parkinson's Disease.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2015 Nov 15; Vol. 195 (10), pp. 4853-60. Date of Electronic Publication: 2015 Oct 09. - Publication Year :
- 2015
-
Abstract
- Foxp3-expressing CD4(+) regulatory T cells (Tregs) are vital for maintaining immune tolerance in animal models of various immune diseases. In the present study, we demonstrated that bee venom phospholipase A2 (bvPLA2) is the major BV compound capable of inducing Treg expansion and promotes the survival of dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. We associated this neuroprotective effect of bvPLA2 with microglial deactivation and reduction of CD4(+) T cell infiltration. Interestingly, bvPLA2 had no effect on mice depleted of Tregs by injecting anti-CD25 Ab. This finding indicated that Treg-mediated modulation of peripheral immune tolerance is strongly involved in the neuroprotective effects of bvPLA2. Furthermore, our results showed that bvPLA2 directly bound to CD206 on dendritic cells and consequently promoted the secretion of PGE2, which resulted in Treg differentiation via PGE2 (EP2) receptor signaling in Foxp3(-)CD4(+) T cells. These observations suggest that bvPLA2-CD206-PGE2-EP2 signaling promotes immune tolerance through Treg differentiation and contributes to the prevention of various neurodegenerative diseases, including Parkinson's disease.<br /> (Copyright © 2015 by The American Association of Immunologists, Inc.)
- Subjects :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine adverse effects
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine pharmacology
Animals
Dinoprostone genetics
Dinoprostone immunology
Disease Models, Animal
Dopaminergic Neurons pathology
Forkhead Transcription Factors genetics
Forkhead Transcription Factors immunology
Lectins, C-Type genetics
Lectins, C-Type immunology
MPTP Poisoning genetics
MPTP Poisoning immunology
MPTP Poisoning pathology
Mannose Receptor
Mannose-Binding Lectins genetics
Mannose-Binding Lectins immunology
Mice
Mice, Transgenic
Microglia immunology
Microglia pathology
Receptors, Cell Surface genetics
Receptors, Cell Surface immunology
T-Lymphocytes, Regulatory pathology
Bee Venoms pharmacology
Dopaminergic Neurons immunology
Insect Proteins pharmacology
MPTP Poisoning prevention & control
Neuroprotective Agents pharmacology
Phospholipases A2 pharmacology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 195
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 26453752
- Full Text :
- https://doi.org/10.4049/jimmunol.1500386