TH17-cell migration from the intestine to the kidney is S1P receptor 1-dependent and drives immune-mediated renal disease

The relationship between microbiota-induced TH17 cells in the intestine and pathogenic TH17responses in autoimmune diseases is still unclear. Here, we report high frequencies of CD4+TH17 cells in the kidneys of patients with ANCA-associated crescentic glomerulonephritis andin a mouse model of crescentic glomerulonephritis. By photoconverting intestinal cells inKaede-transgenic mice, we provide direct evidence for the migration of TH17 cells from theintestine into the inflamed kidney via the CCR6/CCL20 axis. Accordingly, the absence ofintestinal TH 17 cells in germ-free mice and their depletion in antibiotics-treated mice reducedrenal T H17 response and the consecutive tissue injury in glomerulonephritis. In contrast,expansion of intestinal T H17 cells in Citrobacter rodentium infected mice exerted the oppositeeffect. These findings reveal that pathogenic TH17 cells in crescentic glomerulonephritisoriginate from the intestine, migrate into the kidney and drive tissue injury. This might havesignificant implications for the treatment of TH17-driven autoimmune disorders.