CD4 <sup>+</sup> T cells produce GM-CSF and drive immune-mediated glomerular disease by licensing monocyte-derived cells to produce MMP12-Reference-Cited by-同舟云学术

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

Published:2023-03-15 Issue:687 Volume:15 Page:
ISSN:1946-6234
Container-title:Science Translational Medicine
language:en
Short-container-title:Sci. Transl. Med.

Author:

Paust Hans-Joachim¹^ORCID,Song Ning¹^ORCID,De Feo Donatella²^ORCID,Asada Nariaki¹,Tuzlak Selma²^ORCID,Zhao Yu¹³^ORCID,Riedel Jan-Hendrik¹^ORCID,Hellmig Malte¹^ORCID,Sivayoganathan Amirrtavarshni¹^ORCID,Peters Anett¹,Kaffke Anna¹,Borchers Alina¹,Wenzel Ulrich O.¹,Steinmetz Oliver M.¹^ORCID,Tiegs Gisa⁴⁵,Meister Elisabeth¹,Mack Matthias⁶,Kurts Christian⁷^ORCID,von Vietinghoff Sibylle⁸^ORCID,Lindenmeyer Maja T.¹^ORCID,Hoxha Elion¹,Stahl Rolf A. K.¹,Huber Tobias B.¹⁵^ORCID,Bonn Stefan³⁵^ORCID,Meyer-Schwesinger Catherine⁹,Wiech Thorsten¹⁰^ORCID,Turner Jan-Eric¹⁵,Becher Burkhard²^ORCID,Krebs Christian F.¹⁵^ORCID,Panzer Ulf¹⁵^ORCID

Affiliation:

1. III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.

2. Institute of Experimental Immunology, University of Zurich, Zurich 8057, Switzerland.

3. Institute of Medical Systems Biology, Center for Biomedical AI, Center for Molecular Neurobiology Hamburg, Hamburg 20246, Germany.

4. Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf 20246, Germany.

5. Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.

6. Department of Nephrology, University Hospital Regensburg, Regensburg 93042, Germany.

7. Institute of Molecular Medicine and Experimental Immunology, University Hospital Bonn, Bonn 53127, Germany.

8. Nephrology Section, Medical Clinic 1, University Hospital Bonn, Bonn 53127, Germany.

9. Institute of Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.

10. Institute of Pathology, Division of Nephropathology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.

Abstract

GM-CSF in glomerulonephritis Despite 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

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

Link

https://www.science.org/doi/pdf/10.1126/scitranslmed.add6137

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