Growth differentiation factor 15 ameliorates anti-glomerular basement membrane glomerulonephritis in mice

Foteini Moschovaki-Filippidou, Stefanie Steiger, Georg Lorenz, Christoph Schmaderer, Andrea Ribeiro, Ekaterina von Rauchhaupt, Clemens D. Cohen, Hans Joachim Anders, Maja Lindenmeyer, Maciej Lech

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Growth differentiation factor 15 (GDF15) is a member of the transforming growth factor-β (TGF-β) cytokine family and an inflammation-associated protein. Here, we investigated the role of GDF15 in murine anti-glomerular basement membrane (GBM) glomerulonephritis. Glomerulonephritis induction in mice induced systemic expression of GDF15. Moreover, we demonstrate the protective effects for GDF15, as GDF15-deficient mice exhibited increased proteinuria with an aggravated crescent formation and mesangial expansion in anti-GBM nephritis. Herein, GDF15 was required for the regulation of T-cell chemotactic chemokines in the kidney. In addition, we found the upregulation of the CXCR3 receptor in activated T-cells in GDF15-deficient mice. These data indicate that CXCL10/CXCR3-dependent-signaling promotes the infiltration of T cells into the organ during acute inflammation controlled by GDF15. Together, these results reveal a novel mechanism limiting the migration of lymphocytes to the site of inflammation during glomerulonephritis.

Original languageEnglish
Article number6978
Pages (from-to)1-16
Number of pages16
JournalInternational Journal of Molecular Sciences
Volume21
Issue number19
DOIs
StatePublished - 1 Oct 2020
Externally publishedYes

Keywords

  • Chemokines
  • Glomerulonephritis
  • Inflammation
  • Innate immunity
  • T cells

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