The CNS Meninges and the Synovial Joint: Parallel Immunological Structures in Autoimmune Disease

ABSTRACT Autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA) involve complex interactions between local tissues and the immune system. Here, we highlight the immunological parallels between the central nervous system (CNS) meninges and the synovial joint, two sites traditionally considered immune‐privileged. Both harbor resident immune cells and lymphatic vessels and support the formation of tertiary lymphoid organs (TLO) during chronic inflammation. In MS, meningeal TLO contributes to cortical grey matter damage, while in RA, synovial TLO drives joint destruction. T peripheral helper (Tph) cells, a subset of CD4 + T cells, are key players in both conditions by supporting B cell activation and autoantibody production. Epstein–Barr virus (EBV) infection, particularly in B cells within TLO, is implicated in the pathogenesis of both diseases. Targeting EBV‐infected B cells, depleting Tph cells, or disrupting TLO represent promising therapeutic strategies for controlling disease progression and severity in MS and RA.