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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\u2019s 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\u2212CD4+ 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\u2019s disease.<\/jats:p>","DOI":"10.4049\/jimmunol.1500386","type":"journal-article","created":{"date-parts":[[2015,10,10]],"date-time":"2015-10-10T02:23:44Z","timestamp":1444443824000},"page":"4853-4860","source":"Crossref","is-referenced-by-count":85,"title":["Bee Venom Phospholipase A2, a Novel Foxp3+ Regulatory T Cell Inducer, Protects Dopaminergic Neurons by Modulating Neuroinflammatory Responses in a Mouse Model of Parkinson\u2019s Disease"],"prefix":"10.1093","volume":"195","author":[{"given":"Eun Sook","family":"Chung","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Kyung Hee University , Seoul 130-701 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gihyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Kyung Hee University , Seoul 130-701 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Kyung Hee University , Seoul 130-701 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minsook","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Kyung Hee University , Seoul 130-701 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwan-suck","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Kyung Hee University , Seoul 130-701 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunseong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Kyung Hee University , Seoul 130-701 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-joo S","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Biology, University of California Riverside , Riverside, CA 92521"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deok-Sang","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, College of Korean Medicine, Kyung Hee University , Seoul 130-701 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0299-3582","authenticated-orcid":false,"given":"Hyunsu","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Kyung Hee University , Seoul 130-701 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,11,15]]},"reference":[{"key":"2025030704240311200_r1","first-page":"470","article-title":"A phase I study of the safety of honeybee venom extract as a possible treatment for patients with progressive forms of multiple sclerosis","volume":"26","author":"Castro","year":"2005","journal-title":"Allergy Asthma Proc."},{"key":"2025030704240311200_r2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1093\/ecam\/neh070","article-title":"An overview of bee venom acupuncture in the treatment of arthritis","volume":"2","author":"Lee","year":"2005","journal-title":"Evid. 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