Histones of Neutrophil Extracellular Traps (NETs) Activate Brain Pericyte via Dectin-1 in Traumatic Brain Injury

Abstract Brain pericyte is unique and indispensable part of blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms about how pericyte is regulated in damaged brain are largely unknown. Here, we show that neutrophil extracellular traps (NETs) formation induces the appearance of CD11b+ pericytes post TBI. These CD11b+ pericytes subsets are characterized with increased permeability and pro-inflammatory profiles compared to CD11b- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction on brain pericytes in PKC-c-Jun dependent manner, conferring neuroinflammation and BBB dysfunction post TBI. These data indicate that "neutrophil-NETs-pericyte" and "histones-Dectin-1-CD11b" are possible mechanisms for pericyte’s activation and dysfunction. Targeting at NETs formation and Dectin-1 are promising ways for TBI treatments.