Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the involvement of multiple organs [1]. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a disabling and potentially life-threatening complication of SLE, characterized by a range of psychiatric and neurological symptoms, such as depression, cognitive impairment, seizures, and stroke [2,3]. The prevalence of NPSLE is estimated to be between 37 and 95% of patients with SLE [[4], [5], [6]]. Treatment options for NPSLE are often limited and challenging [3,7]. Therefore, further research is crucial to understanding the mechanism and improving the treatment of NPSLE.

Previous studies have demonstrated the involvement of T cells in the pathogenesis of SLE [[8], [9], [10]]. It has been reported that inappropriate lymphocytes, especially CD4+ T cells, homing to tissues may exacerbate many SLE-related symptoms, including NPSLE [[11], [12], [13]]. Fingolimod (FTY720), a sphingosine-1-phosphate (S1P) receptor modulator, selectively confines lymphocytes in lymph nodes and attenuates NPSLE-related behavioral deficits in mice [14,15]. On the other hand, previous studies showed that depletion of autoantibody titers or B cells could not prevent NPSLE-like symptoms in MRL/lpr mice [[16], [17], [18], [19]]. Thus, CD4+ T cells may be a key factor that contributes to the pathogenesis of NPSLE. However, whether and how lupus CD4+ T cells lead to NPSLE remains obscure.

Therefore, this study aims to identify the role of choroid plexus (CP)-resident CD4+ T cells in NPSLE-like symptoms in mice. We selectively depleted CP-resident CD4+ T cells in MRL/lpr mice and intracerebroventricularly transferred lupus CD4+ T cells into the brain in C57BL/6 mice. NPSLE-related symptoms were evaluated using behavioral tests, immunofluorescence, transmission electron microscopy, and other techniques.