期刊
IMMUNITY
卷 45, 期 5, 页码 1078-1092出版社
CELL PRESS
DOI: 10.1016/j.immuni.2016.10.020
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类别
资金
- Deutsche Forschungsgemeinschaft [SFB 1192]
- Deutsche Nierenstiftung
- Deutsche Gesellschaft fur Nephrologie
- Werner-Otto-Foundation
- The Francis Crick Institute [10159] Funding Source: researchfish
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.
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