Pericytes regulate vascular immune homeostasis in the CNS

• DOI: 10.1073/pnas.2016587118
• Publication Date: 2021-03-02T20:50:57Z
• Authors: Orsolya Török; Bettina Schreiner; Johanna Schaffenrath; Hsing-Chuan Tsai; Upasana Maheshwari; Sebastian A. Stifter; Christina Welsh; Ana Amorim; Sucheta Sridhar; Sebastian G. Utz; Wiebke Mildenberger; Sina Nassiri; Mauro Delorenzi; Adriano Aguzzi; May H. Han; Melanie Greter; Burkhard Becher; Annika Keller
• Keywords: Pericyte; Mural cell; Proinflammatory cytokine; Homeostasis; Myelin oligodendrocyte glycoprotein

Pericytes regulate the development of organ-specific characteristics brain vasculature such as blood-brain barrier (BBB) and astrocytic end-feet. Whether pericytes are involved in control leukocyte trafficking adult central nervous system (CNS), a process tightly regulated by CNS vasculature, remains elusive. Using pericyte-deficient mice (Pdgfbret/ret ), we show that limit infiltration into during homeostasis autoimmune neuroinflammation. The permissiveness toward Pdgfbret/ret inversely correlates with vessel pericyte coverage. Upon induction experimental encephalomyelitis (EAE), die severe atypical EAE, which can be reversed fingolimod, indicating mortality is due to massive influx immune cells brain. Additionally, administration anti-VCAM-1 anti-ICAM-1 antibodies reduces diminishes severity EAE symptoms mice, proinflammatory endothelium absence facilitates exaggerated Furthermore, presence myelin peptide-specific peripheral T ;2D2tg leads spontaneous neurological paralleled leukocytes These findings indicate intrinsic changes within promote neuroinflammatory disorder.