Potential Mechanism of Paraquat-Induced Blood-Brain Barrier Disruption: IL-17A as a Risk Accelerator for Disrupting bEnd.3 Cells Tight Junction.

Paraquat (PQ) is a globally and widely used high-residue herbicide, also regarded as a potential environmental risk factor for neurodegenerative diseases (NDs). However, how PQ exerts neurotoxicity remains a mystery. The blood-brain barrier (BBB) plays a crucial role in communicating between the central nervous system (CNS) and the peripheral blood. In this article, the core genes, which were mainly based on the potential targets for PQ, MPTP, and Diquat chemicals from the CTD database, intersected with the potential targets related to the symptoms of NDs from databases GeneCards and OMIM. Then GO and KEGG enrichments revealed IL-17A was involved. After being treated with PQ, in vivo, C57BL/6J mice showed low mood and decreased learning and memory abilities. Pathologically, there were captured CD3 and its CD4/8 subsets, as well as IL-17A. Surprisingly, T cells in peripheral blood and spleen that responded to PQ gradually leaned towards Th17 cells and secreted IL-17A. Therefore, it is highly suspected that IL-17A plays a role in disrupting the BBB. In vitro, constructed with recombinant IL-17A, and single-PQ or mixtures (recombinant IL-17A and PQ) to bEnd.3 cells, which together showed that IL-17A is a helper for PQ to aggravately disrupt the BBB. In vivo, mice were treated with IL-17A neutralizing antibodies, which effectively inhibited the permeability damage of the BBB. And in the brain parenchyma, the expression of IL-17A also decreased. In summary, the first to respond to PQ were T cells in the peripheral blood, mainly secreting IL-17A, which also acted as a risk factor disrupting the BBB and assists PQ and other factors in infiltrating parenchyma.