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Summary Vascular smooth muscle cells (VSMCs) have been widely recognized as key players in regulating blood-brain barrier (BBB) function, and their roles are unclear in ischemic stroke. Myosin phosphatase target subunit 1 (MYPT1) is essential for VSMC contraction and maintaining healthy vasculature. We generated VSMC-specific MYPT1 knockout (MYPT1SMKO) mice and cultured VSMCs infected with Lv-shMYPT1 to explore phenotypic switching of VSMCs and the accompanied impacts on BBB integrity. We found that MYPT1 deficiency induced phenotypic switching of synthetic VSMCs, which aggravated BBB disruption. Proteomic analysis identified evolutionarily conserved signaling intermediates in Toll pathways (ECSIT) as a downstream molecule that promotes activation of synthetic VSMCs and contributed to IL-6 expression. Knocking down ECSIT rescued phenotypic switching of VSMCs and BBB disruption. Additionally, inhibition of IL-6 decreased BBB permeability. These findings reveal that MYPT1 deficiency activated phenotypic switching of synthetic VSMCs and induced BBB disruption through ECSIT-IL-6 signaling after ischemic stroke., Graphical abstract, Highlights • MYPT1 deficiency induces activation of synthetic VSMCs and aggravates BBB disruption • Synthetic VSMCs release more IL-6 to destroy BBB in a contact-independent way • MYPT1-ECSIT-IL-6 signaling pathway regulates synthetic VSMC-mediated BBB disruption, Immunology; Molecular physiology; Cell biology; Proteomics

Adult hippocampal neurogenesis involves proliferation, survival, differentiation and integration of newborn neurons into pre-existing neuronal networks. Although its functional significance in the central nervous system (CNS) has not comprehensively elucidated, adult neurogenesis has been attributed a role in cognition, learning and memory. There is a growing body of evidence that CNS resident as well as peripheral immune cells participate in regulating hippocampal adult neurogenesis. Microglial cells are closely associated with neural stem/progenitor cell (NSPC) in the neurogenic niche engaged in a bidirectional communication with neurons, which may be important for adult neurogenesis. Microglial and neuronal crosstalk is mediated in part by CX3CL1/CX3CR1 signaling and a disruption in this pathway has been associated with impaired neurogenesis. It has been also reported that microglial neuroprotective or neurotoxic effects in adult neurogenesis occur in a context-dependent manner. Apart from microglia other brain resident and peripheral immune cells including pericytes, perivascular macrophages, mast cells and T-cells also modulate this phenomenon. It is worth mentioning that under some physiological circumstances such as normal aging there is a significant decrease in hippocampal neurogenesis. A role for innate and adaptive immune system in adult neurogenesis has been also reported during aging. Here, we review the current evidence regarding neuro-immune interactions in the regulation of neurogenesis under distinct conditions, including aging.