Pericytes regulate the development of organ-specific characteristics of the brain vasculature such as the blood–brain barrier (BBB) and astrocytic end-feet. Whether pericytes are involved in the control of leukocyte trafficking in the adult central nervous system (CNS), a process tightly regulated by CNS vasculature, remains elusive. Using adult pericyte-deficient mice (Pdgfb^ret/ret), we show that pericytes limit leukocyte infiltration into the CNS during homeostasis and autoimmune neuroinflammation. The permissiveness of the vasculature toward leukocyte trafficking in Pdgfb^ret/ret mice inversely correlates with vessel pericyte coverage. Upon induction of experimental autoimmune encephalomyelitis (EAE), pericyte-deficient mice die of severe atypical EAE, which can be reversed with fingolimod, indicating that the mortality is due to the massive influx of immune cells into the brain. Additionally, administration of anti-VCAM-1 and anti–ICAM-1 antibodies reduces leukocyte infiltration and diminishes the severity of atypical EAE symptoms of Pdgfb^ret/ret mice, indicating that the proinflammatory endothelium due to absence of pericytes facilitates exaggerated neuroinflammation. Furthermore, we show that the presence of myelin peptide-specific peripheral T cells in Pdgfb^ret/ret;2D2^tg mice leads to the development of spontaneous neurological symptoms paralleled by the massive influx of leukocytes into the brain. These findings indicate that intrinsic changes within brain vasculature can promote the development of a neuroinflammatory disorder.

周细胞调节脑血管系统器官特异性特征的发育，例如血脑屏障 (BBB) 和星形细胞末端。周细胞是否参与控制成人中枢神经系统 (CNS) 中的白细胞运输，这是一个受 CNS 脉管系统严格调节的过程，仍然难以捉摸。使用成年周细胞缺陷小鼠 ( Pdgfb ^ret/ret )，我们表明周细胞在体内平衡和自身免疫性神经炎症期间限制白细胞浸润到中枢神经系统。Pdgfb ^{ret/ret 中}脉管系统对白细胞运输的许可小鼠与血管周细胞覆盖率呈负相关。在诱导实验性自身免疫性脑脊髓炎 (EAE) 后，周细胞缺陷小鼠死于严重的非典型 EAE，这可以用芬戈莫德逆转，表明死亡率是由于免疫细胞大量流入大脑。此外，给予抗 VCAM-1 和抗 ICAM-1 抗体可减少白细胞浸润并减轻Pdgfb ^ret/ret小鼠非典型 EAE 症状的严重程度，表明由于周细胞缺失导致的促炎内皮促进了神经炎症的加剧。此外，我们表明Pdgfb ^{ret/ret 中}存在髓鞘肽特异性外周 T 细胞；2D2 ^tg小鼠导致自发性神经症状的发展，同时白细胞大量涌入大脑。这些发现表明脑血管系统内的内在变化可以促进神经炎症性疾病的发展。