In the present study, we examined whether bee venom phospholipase 2 (bvPLA2) promotes the survival of dopaminergic (DA) neurons in the MPTP-induced mouse model of Parkinson’s disease (PD). Treatment of bvPLA2 prevented degeneration of DA neurons in the substantia nigra (SN). This nueroprotection of bvPLA2 associated with the suppression of microglia and inhibition of infiltration of CD4+ T cells into the SN. Additionally, CD4+CD25+Foxp3+ Tregs were significantly increased in vivo and in vitro after treatment of bvPLA2. The increased proportion of Tregs by bvPLA2 treatement remained highly suppressive ex vivo. To determine whether this neuroprotective effects of bvPLA2 associated with Tregs, we used transgenic DEREG (depletion of regulatory T cells) mice, which express a diphtheria toxin receptor under control of the Foxp3 locus, allowing selective depletion of Foxp3+ Tregs. Interestingly, bvPLA2 treatment did not prevent MPTP neurotoxicity in mice depleted of Tregs by dt treatment. Therefore, our present studies indicate that the neuro-protective effect of bvPLA2 might be associated with its anti-inflammatory properties resulting from modulation of peripheral immune tolerance by Tregs.
- Copyright © 2013 by The American Association of Immunologists, Inc.