Meningeal lymphoid structures are activated under acute and chronic spinal cord pathologies

Tertiary lymphoid structures (TLS) are organized aggregates of B and T cells formed ectopically during different life periods in response to inflammation, infection, or cancer. Here, we describe formation of structures reminiscence of TLS in the spinal cord meninges under several central nervous system (CNS) pathologies. Following acute spinal cord injury, B and T lymphocytes locally aggregate within the meninges to form TLS, which continue to accumulate during the late phase of repair, with a negative impact on subsequent pathological conditions, such as experimental autoimmune encephalomyelitis. Using a chronic model of spinal cord pathology, the mSOD1 mouse model of amyotrophic lateral sclerosis, we further showed by single cell RNA-sequencing that a meningeal lymphocyte niche forms, with a unique organization and activation state, including accumulation of pre-B cells in the spinal cord meninges. Such a response was not found in the CNS-draining cervical lymph nodes. The present findings suggest that a unique immune response develops in the meninges during various neurological pathologies in the CNS, a reflection of its immune privileged nature.