Proposed CSF drainage pathway through the murine CP. (A) Sagittal view of the mouse brain showing CSF circulation (blue) and proposed outflow across the CP to nasal soft tissue and cribriform/nasal lymphatic vessels (green) that drain into CLNs (Jin et al., 2025; Yoon et al., 2024; Decker et al., 2022; Papadopoulos et al., 2025). Pathways include the following: (1) CSF is secreted from choroid plexus; (2) CSF exits from ventricles into subarachnoid space, (3) flows along base brain, and (4) effluxes through the CP lymphatics near olfactory nerve bundle environment; and (5a) olfactory mucosa lymphatics drain into nasopharyngeal lymphatic plexus and into (6) CLNs for antigen presentation and T cell activation. Alternatively, deep respiratory mucosal lymphatics (5b) drain through the hard palate and nasal sidewall to submandibular lymph nodes (or superficial CLNs) (6). (B) Sagittal schematic of the CP region highlights olfactory nerve bundles (fila olfactoria), arachnoid extensions of the subarachnoid space, and lymphatics that receive antigens and immune cells. (C) cpPME contains olfactory nerve (ON) bundles ensheathed by discontinuous arachnoid-like tissue, DCs, macrophages, and cpLVs that sample CSF, waste, and antigens. (D) Antigen-loaded DCs traffic to CLNs, where they present CNS antigens to CD4⁺ T cells, driving proliferation of CNS-targeting T cells that can migrate to the brain and influence neuroinflammation. Panels A and B are modified from Laaker et al. (2023).