Moreover, independent lines of evidence support a pro-inflammatory role for KYN: 1) the accumulation of KYN in sera and CD8+ T cells preceded the onset of autoantibody production and GN disease onset in SLE in B6.TC/Rab4AQ72L mice; 2) KYN itself enhanced CD4+ over CD8+ T-cell development in primary B6 mouse splenocytes; 3) KYN activated mTOR in B cells and expanded plasma cells in primary B6 mouse splenocytes; and 4) Rab4A formed a positive feed-back loop with mTOR activation and expression of metabolite-transporting CD98 receptor during lupus pathogenesis in mice and patients with SLE. This evidence concerns the gene RAB4A and ganglioneuroma.