We show that MSCT rescues impaired synaptic density and alleviates depression-like behaviors in young (5- to 8-week-old) lupus mice by reducing systemic T helper 1 (Th1) cell–derived IFN-γ levels to inhibit neuronal JAK/STAT1 signaling and downstream CCL8 expression and then inhibit neuron-coordinated synapse elimination by microglia in the brain. Here, CCL8 is linked to systemic lupus erythematosus.