Choroid plexus tertiary lymphoid structures in lupus: a novel neuro-immune interface. Mus musculus

The central nervous system manifestations of systemic lupus erythematosus (SLE) remain poorly understood, confounding physician treatment options and leaving patients with little options beyond empirical remedies. We utilized a well-established model of both the systemic and neuropsychiatric manifestations of SLE in an attempt to further understand which immune effectors may be responsible for central nervous system (CNS) disease. We found that a mixed cellular infiltrate in the choroid plexus of these mice represented a tertiary lymphoid structure with in-situ somatic hypermutation and class switch recombination. We further found that this process was driven by cytokine signaling sourced within the CNS that could be abrogated by treatment with biological therapeutics. Therefore, inconsistencies in previous work to determine which neuropathic autoantibodies are involved in the progression of neuropsychiatric lupus may have been lacking, as the source of these autoantibodies are intra-cranial, with limited systemic distribution. Overall design: Choroid plexus mRNA profiles of 12 week old MRL/lpr (6 samples) and MRL/+ mice (3 samples) and 16 week old MRL/lpr (6 samples) and MRL/+ (3 samples) sequenced with HiSeq2500.