TY - JOUR
T1 - Growth differentiation factor 15 ameliorates anti-glomerular basement membrane glomerulonephritis in mice
AU - Moschovaki-Filippidou, Foteini
AU - Steiger, Stefanie
AU - Lorenz, Georg
AU - Schmaderer, Christoph
AU - Ribeiro, Andrea
AU - von Rauchhaupt, Ekaterina
AU - Cohen, Clemens D.
AU - Anders, Hans Joachim
AU - Lindenmeyer, Maja
AU - Lech, Maciej
N1 - Publisher Copyright:
© 2020, MDPI AG. All rights reserved.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
KW - Chemokines
KW - Glomerulonephritis
KW - Inflammation
KW - Innate immunity
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=85091594902&partnerID=8YFLogxK
U2 - 10.3390/ijms21196978
DO - 10.3390/ijms21196978
M3 - Article
C2 - 32977372
AN - SCOPUS:85091594902
SN - 1661-6596
VL - 21
SP - 1
EP - 16
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 19
M1 - 6978
ER -