Immune interactions at the murine cpPME during neuroinflammation. Schematic of CSF efflux, immune surveillance, and perineural microenvironment. CSF carrying antigens, waste, and pathogens drains alongside olfactory nerve bundles into CP lymphatic vessels. Antigen-presenting cells (APCs), such as DCs, migrate through this route to CLNs. Olfactory nerve fibroblasts and macrophages in the olfactory nerve bundles shape the extracellular matrix and provide signals for immune cell adhesion and migration. Lymphatic vessels express adhesion molecules (ICAM-1, VCAM-1) and chemokines (CCL19/21, CCL2) that recruit DCs, monocytes, and T cells. M2 macrophages in perineural niche can contribute tolerogenic signals (IL-10, TGF-β, PD-L1), while Th1 cells provide inflammatory cues (IFN-γ), which drives immunoregulatory remodeling including upregulation of PD-L1 and MHC-II on immune cells and lymphatic vessels. Bone marrow niches undergoing elevated myelopoiesis within the skull connect to olfactory nerve bundles through channels, potentially supplying immune cells to nearby regions.