Cribriform Plate Microenvironment Assembles a Suppressive Myeloid Network during EAE-induced Neuroinflammation

Abstract

During neuroinflammation, CD11c+CD11b+ myeloid cells accumulate at the cribriform plate, a key cerebrospinal fluid (CSF) and antigen outflow site in mice. At this site, podoplanin (PDPN)-expressing cells, including lymphatic vessels and meningeal layers, expand to create a distinct drainage microenvironment. In this study we sought to characterize myeloid cells which populate this region using a mouse model of neuroinflammation, experimental autoimmune encephalomyelitis (EAE). Utilizing a combination of immunohistochemistry, flow cytometry, and scRNAseq, we report that macrophages and dendritic cells (DCs) from this region display unique expressional signatures related to tolerance, cell death, and reduced inflammatory profile. Together this data supports that myeloid retention at the cribriform plate and olfactory bulb meninges promotes a local immunosuppressive environment.