Abstract
SummaryTh17 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.
Highlights
CD4+ T cells are critical for defense against a wide array of invading microbes and pathogens but are major drivers of autoimmune diseases
To determine the composition of T cell subsets in antineutrophil cytoplasmatic antibody (ANCA)-associated GN, we analyzed cells isolated from human renal biopsies by flow cytometry
Th17 cells can be distinguished from other CD4+ T cells via the expression of the transcription factor RORgt
Summary
CD4+ T cells are critical for defense against a wide array of invading microbes and pathogens but are major drivers of autoimmune diseases. Th17 cells are characterized by their key transcription factors RORgt and STAT3 (Ivanov et al, 2006; Nurieva et al, 2007), the production of the cytokines IL-17A, IL-17F, IL22 and GM-CSF (Codarri et al, 2011; Zenewicz et al, 2007), and high expression of CCR6 (Acosta-Rodriguez et al, 2007). Today, their central role in the pathogenesis of several autoimmune diseases is clearly established (Gaffen et al, 2014)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
