CD4+ T cells produce GM-CSF and drive immune-mediated glomerular disease by licensing monocyte-derived cells to produce MMP12

Sci Transl Med. 2023 Mar 15;15(687):eadd6137. doi: 10.1126/scitranslmed.add6137. Epub 2023 Mar 15.

Abstract

GM-CSF in glomerulonephritisDespite glomerulonephritis being an immune-mediated disease, the contributions of individual immune cell types are not clear. To address this gap in knowledge, Paust et al. characterized pathological immune cells in samples from patients with glomerulonephritis and in samples from mice with the disease. The authors found that CD4+ T cells producing granulocyte-macrophage colony-stimulating factor (GM-CSF) licensed monocytes to promote disease by producing matrix metalloproteinase 12 and disrupting the glomerular basement membrane. Targeting GM-CSF to inhibit this axis reduced disease severity in mice, implicating this cytokine as a potential therapeutic target for patients with glomerulonephritis. -CM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes
  • Glomerulonephritis* / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor* / pharmacology
  • Matrix Metalloproteinase 12 / metabolism
  • Mice
  • Monocytes / metabolism

Substances

  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Matrix Metalloproteinase 12