Autoimmune Renal Disease Is Exacerbated by S1P-Receptor-1-Dependent Intestinal Th17 Cell Migration to the Kidney

Immunity. 2016 Nov 15;45(5):1078-1092. doi: 10.1016/j.immuni.2016.10.020.


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.

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • Chemotaxis, Leukocyte / immunology*
  • Citrobacter rodentium
  • Disease Models, Animal
  • Enterobacteriaceae Infections / immunology
  • Flow Cytometry
  • Glomerulonephritis / immunology*
  • Humans
  • Intestines / immunology
  • Kidney / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Real-Time Polymerase Chain Reaction
  • Receptors, Lysosphingolipid / immunology*
  • Sphingosine-1-Phosphate Receptors
  • Th17 Cells / immunology*


  • Receptors, Lysosphingolipid
  • S1PR1 protein, human
  • S1pr1 protein, mouse
  • Sphingosine-1-Phosphate Receptors