HMGB1 A Box protects neurons by potently inhibiting both microglia and T cell-mediated inflammation in a mouse Parkinson's Disease model.

In the subacute Parkinson's disease mice model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), injection of HMGB1 competitive inhibitor protein HMGB1 A Box and the Ethyl pyruvate which inhibit the release of HMGB1 from cells, restored the number of dopaminergic neurons and TH+ fibers in the SN and striatum. Our data show that A Box up regulated CD200-CD200R signal of microglia, inhibit the activation of microglia mediated by HMGB1 and the production of TNF-α IL-1β and IL-6 in vivo and in vitro mixed culture system. Microglia overexpressing CD200R produced less inflammatory chemokines and reduced the loss of TH+ neurons. In addition, HMGB1 A Box decreased the level of CCL5 and significantly inhibited the infiltration of almost all T cells including Th17 and the proportion of Th17 in CD4+ T cells. In vitro MPP+ induced model and HMGB1 stimulated mesencephalic cell system, activated microglia induced the differentiation of Naive T cells to Th17, and A Box significantly inhibited this process. To sum up, our results show that HMGB1 A Box targeting HMGB1, which effectively reduces the activation of microglia in MPTP PD model by restoring CD200-CD200R inhibition signal, inhibit microglia mediated neuroinflammation and the differentiation of T cells to Th17.