Histones of Neutrophil Extracellular Traps Induce CD11b Expression in Brain Pericytes Via Dectin-1 after Traumatic Brain Injury

• DOI: 10.1007/s12264-022-00902-0
• Publication Date: 2022-07-12T08:34:01Z
• Authors: Yang-Wuyue Liu; Jingyu Zhang; Wanda Bi; Mi Zhou; Jiabo Li; Tiantian Xiong; Nan Yang; Li Zhao; Xing Chen; Yuanguo Zhou; Wenhui He; Teng Yang; Hao Wang; Lunshan Xu; Shuang-Shuang Dai
• Keywords: Histones; 0303 health sciences; 03 medical and health sciences; Blood-Brain Barrier; Brain Injuries, Traumatic; Brain; Humans; Lectins, C-Type; Pericytes; Extracellular Traps; 3. Good health

The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b+ pericytes after TBI. These CD11b+ pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.