These results suggest that the activation of 25% PPARγ expression in PpargC/− mice promotes S1P1 expression in splenocytes and prevents B-cell hyperactivation by attenuating Th17 polarization; these activities collectively contribute to the decrease in spleen weight and, finally, amelioration of the SLE-like autoimmune disease. The gene discussed is PPARG; the disease is systemic lupus erythematosus.