TY - JOUR
T1 - CXCL5 drives neutrophil recruitment in TH17-mediated GN
AU - Disteldorf, Erik M.
AU - Krebs, Christian F.
AU - Paust, Hans Joachim
AU - Turner, Jan Eric
AU - Nouailles, Geraldine
AU - Tittel, André
AU - Meyer-Schwesinger, Catherine
AU - Stege, Gesa
AU - Brix, Silke
AU - Velden, Joachim
AU - Wiech, Thorsten
AU - Helmchen, Udo
AU - Steinmetz, Oliver M.
AU - Peters, Anett
AU - Bennstein, Sabrina B.
AU - Kaffke, Anna
AU - Llanto, Chrystel
AU - Lira, Sergio A.
AU - Mittrücker, Hans Willi
AU - Stahl, Rolf A.K.
AU - Kurts, Christian
AU - Kaufmann, Stefan H.E.
AU - Panzer, Ulf
N1 - Publisher Copyright:
Copyright © 2015 by the American Society of Nephrology.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Neutrophil trafficking to sites of inflammation is essential for the defense against bacterial and fungal infections, but also contributes to tissue damage in TH17-mediated autoimmunity. This process is regulated by chemokines, which often show an overlapping expression pattern and function in pathogen-and autoimmune-induced inflammatory reactions. Using a murine model of crescentic GN, we show that the pathogenic TH17/ IL-17 immune response induces chemokine (C-X-C motif) ligand 5 (CXCL5) expression in kidney tubular cells, which recruits destructive neutrophils that contribute to renal tissue injury. By contrast, CXCL5 was dispensable for neutrophil recruitment and effective bacterial clearance in a murine model of acute bacterial pyelonephritis. In line with these findings, CXCL5 expression was highly upregulated in the kidneys of patients with ANCA-associated crescentic GN as opposed to patients with acute bacterial pyelonephritis. Our data therefore identify CXCL5 as a potential therapeutic target for the restriction of pathogenic neutrophil infiltration in TH17-mediated autoimmune diseases while leaving intact the neutrophil function in protective immunity against invading pathogens.
AB - Neutrophil trafficking to sites of inflammation is essential for the defense against bacterial and fungal infections, but also contributes to tissue damage in TH17-mediated autoimmunity. This process is regulated by chemokines, which often show an overlapping expression pattern and function in pathogen-and autoimmune-induced inflammatory reactions. Using a murine model of crescentic GN, we show that the pathogenic TH17/ IL-17 immune response induces chemokine (C-X-C motif) ligand 5 (CXCL5) expression in kidney tubular cells, which recruits destructive neutrophils that contribute to renal tissue injury. By contrast, CXCL5 was dispensable for neutrophil recruitment and effective bacterial clearance in a murine model of acute bacterial pyelonephritis. In line with these findings, CXCL5 expression was highly upregulated in the kidneys of patients with ANCA-associated crescentic GN as opposed to patients with acute bacterial pyelonephritis. Our data therefore identify CXCL5 as a potential therapeutic target for the restriction of pathogenic neutrophil infiltration in TH17-mediated autoimmune diseases while leaving intact the neutrophil function in protective immunity against invading pathogens.
UR - http://www.scopus.com/inward/record.url?scp=84924143504&partnerID=8YFLogxK
U2 - 10.1681/ASN.2013101061
DO - 10.1681/ASN.2013101061
M3 - Article
C2 - 24904089
AN - SCOPUS:84924143504
SN - 1046-6673
VL - 26
SP - 55
EP - 66
JO - Journal of the American Society of Nephrology : JASN
JF - Journal of the American Society of Nephrology : JASN
IS - 1
ER -