T helper type 17 cells in immune-mediated glomerular disease

Nat Rev Nephrol. 2017 Oct;13(10):647-659. doi: 10.1038/nrneph.2017.112. Epub 2017 Aug 7.

Abstract

CD4+ T cells are important drivers of tissue damage in immune-mediated renal diseases, such as anti-glomerular basement membrane glomerulonephritis, anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis. The discovery of a distinct, IL-17-producing CD4+ T-cell lineage termed T helper type 17 (TH17) cells has markedly advanced current understanding of the pathogenic mechanisms of organ-specific immunity and the pathways that lead to target organ damage. TH17 cells are characterized by the expression of the transcription factor RORγt, the production of the pro-inflammatory cytokines IL-17A, IL-17F, IL-22, and high expression of the chemokine receptor C-C-motif chemokine receptor 6 (CCR6). An emerging body of evidence from experimental models and human studies supports a key role for these cells in the development of renal damage, and has led to the identification of targets to inhibit the production of TH17 cells in the intestine, their migration, or their actions within the kidney. Here, we describe the identification, regulation, and function of TH17 cells and their associated pathways in immune-mediated kidney diseases, with a particular focus on the mechanisms underlying renal tissue injury. We also discuss the rationale for the translation of these findings into new therapeutic approaches in patients with autoimmune kidney disease.

Publication types

  • Review

MeSH terms

  • Autoimmune Diseases / immunology*
  • Glomerulonephritis / immunology*
  • Humans
  • Inflammation / immunology*
  • Interleukin-17 / immunology*
  • Microbiota
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • Interleukin-17