A potential clue of IL-17A as a helper assist paraquat and T cell infiltration into brain parenchyma

Abstract

Paraquat (PQ), a globally widely used and highly residual herbicide, is one of the potential environmental risk factors for neurodegenerative diseases (NDs). Before exerting neurotoxicity, however, PQ needs to break through the blood-brain barrier (BBB), how it penetrates the BBB and reaches the brain parenchyma remains a mystery. Recently, peripheral T cells and cytokine infiltrates into the brain have been involved in the development of NDs. But, the main reason for the infiltrating is not yet unrevealed. BBB plays a crucial role in the communication of T cells between the central nervous system (CNS) and the peripheral. Hence, whether T cells and their cytokines serve as core assistants to assist PQ infiltrating the BBB exerting neurotoxicity, in this article, C57BL/6J mice treated with PQ experienced down emotion and learning and memory abilities decreased. Pathologically, neurons and microglia respectively exhibit selective spatial damage and hyperresponsiveness. Simultaneously there were capture the traces of CD3 and its subsets of CD4/8, as well as IL-17A. Surprisingly, the response of T cells from peripheral blood and spleen to PQ gradually leans towards Th17 cells and secretes IL-17A. Therefore, it is highly suspected that IL-17A plays a role in disrupting the BBB. In vitro, bEnd.3 cells were specifically constructed with IL-17A, and PQ or mixture revealed IL-17A takes part in PQ-induced BBB disruption. Altogether, PQ responds to peripheral T cells to react and secrete IL-17A, which destroys BBB and assists PQ and T cells or other factors in infiltrating brain parenchyma.