Autoimmune renal disease is exacerbated by S1P-receptor-1-dependent intestinal Th17 cell migration to the kidneyMore about Open Access at the Crick
Authors listChristian F Krebs Hans-Joachim Paust Sonja Krohn Tobias Koyro Silke R Brix Jan-Hendrik Riedel Patricia Bartsch Thorsten Wiech Catherine Meyer-Schwesinger Jiabin Huang Nicole Fischer Philipp Busch Hans-Willi Mittrücker Ulrich Steinhoff Gitta Stockinger Laura Garcia Perez Ulrich O Wenzel Matthias Janneck Oliver M Steinmetz Nicola Gagliani Rolf AK Stahl Samuel Huber Jan-Eric Turner Ulf Panzer
Th17 cells are most abundant in the gut, where their presence depends on the intestinal microbiota. Here, we examined whether intestinal Th17 cells contribute to extra-intestinal Th17 responses in autoimmune kidney disease. We found high frequencies of Th17 cells in the kidneys of patients with antineutrophil cytoplasmatic antibody (ANCA)-associated glomerulonephritis. We utilized photoconversion of intestinal cells in Kaede mice to track intestinal T cell mobilization upon glomerulonephritis induction, and we found that Th17 cells egress from the gut in a S1P-receptor-1-dependent fashion and subsequently migrate to the kidney via the CCL20/CCR6 axis. Depletion of intestinal Th17 cells in germ-free and antibiotic-treated mice ameliorated renal disease, whereas expansion of these cells upon Citrobacter rodentium infection exacerbated pathology. Thus, in some autoimmune settings, intestinal Th17 cells migrate into target organs, where they contribute to pathology. Targeting the intestinal Th17 cell "reservoir" may present a therapeutic strategy for these autoimmune disorders.