Paust, Hans-Joachim and Song, Ning and De Feo, Donatella and Asada, Nariaki and Tuzlak, Selma and Zhao, Yu and Riedel, Jan-Hendrik and Hellmig, Malte and Sivayoganathan, Amirrtavarshni and Peters, Anett and Kaffke, Anna and Borchers, Alina and Wenzel, Ulrich O. and Steinmetz, Oliver M. and Tiegs, Gisa and Meister, Elisabeth and Mack, Matthias and Kurts, Christian and von Vietinghoff, Sibylle and Lindenmeyer, Maja T. and Hoxha, Elion and Stahl, Rolf A. K. and Huber, Tobias B. and Bonn, Stefan and Meyer-Schwesinger, Catherine and Wiech, Thorsten and Turner, Jan-Eric and Becher, Burkhard and Krebs, Christian F. and Panzer, Ulf (2023) CD4+T cells produce GM-CSF and drive immune- mediated glomerular disease by licensing monocyte- derived cells to produce MMP12. SCIENCE TRANSLATIONAL MEDICINE, 15 (687): eadd6137. ISSN 1946-6234, 1946-6242
Full text not available from this repository. (Request a copy)Abstract
Glomerulonephritis is a group of immune-mediated diseases that cause inflammation within the glomerulus and adjacent compartments of the kidney and is a major cause of end-stage renal disease. T cells are among the main drivers of glomerulonephritis. However, the T cell subsets, cytokine networks, and downstream effector mechanisms that lead to renal tissue injury are largely unknown, which has hindered the development of targeted therapies. Here, we identify a population of granulocyte-macrophage colony-stimulating factor (GMCSF)-producing T cells that accumulates in the kidneys of patients with antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, infiltrates the renal tissue in a mouse model of glomerulonephritis, and promotes tissue destruction and loss of renal function. Mechanistically, we show that GM-CSF-producing T cells license monocyte-derived cells to produce matrix metalloproteinase 12 (MMP12), which cleaves components of the glomerular basement membrane and exacerbates renal pathology. Moreover, targeting GM-CSF or MMP12 reduced disease severity in mice with glomerulonephritis. Together, these findings provide a mechanistic rationale for the immunopathology of T cell-mediated diseases and identify this GM-CSF monocyte- derived cells-MMP12 axis as a promising therapeutic target for the treatment of glomerulonephritis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COLONY-STIMULATING FACTOR; GROWTH-FACTOR; IFN-GAMMA; MECHANISMS; RESPONSES; INVASION; SYSTEM; INJURY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2024 09:04 |
| Last Modified: | 09 Apr 2024 09:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60717 |
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