CCR6 recruits regulatory T cells and Th17 cells to the kidney in glomerulonephritis.
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CCR6 recruits regulatory T cells and Th17 cells to the kidney in glomerulonephritis. / Turner, Jan Eric; Paust, Hans-Joachim; Steinmetz, Oliver; Peters, Anett; Riedel, Jan-Hendrik; Erhardt, Annette; Wegscheid, Claudia; Velden, Joachim; Fehr, Susanne; Mittrücker, Hans Willi; Tiegs, Gisa; Stahl, Rolf A.K.; Panzer, Ulf.
in: J AM SOC NEPHROL, Jahrgang 21, Nr. 6, 6, 2010, S. 974-985.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - CCR6 recruits regulatory T cells and Th17 cells to the kidney in glomerulonephritis.
AU - Turner, Jan Eric
AU - Paust, Hans-Joachim
AU - Steinmetz, Oliver
AU - Peters, Anett
AU - Riedel, Jan-Hendrik
AU - Erhardt, Annette
AU - Wegscheid, Claudia
AU - Velden, Joachim
AU - Fehr, Susanne
AU - Mittrücker, Hans Willi
AU - Tiegs, Gisa
AU - Stahl, Rolf A.K.
AU - Panzer, Ulf
PY - 2010
Y1 - 2010
N2 - T cells recruited to the kidney contribute to tissue damage in crescentic and proliferative glomerulonephritides. Chemokines and their receptors regulate T cell trafficking, but the expression profile and functional importance of chemokine receptors for renal CD4+ T cell subsets are incompletely understood. In this study, we observed that renal FoxP3+CD4+ regulatory T cells (Tregs) and IL-17-producing CD4+ T (Th17) cells express the chemokine receptor CCR6, whereas IFNgamma-producing Th1 cells are CCR6-. Induction of experimental glomerulonephritis (nephrotoxic nephritis) in mice resulted in upregulation of the only CCR6 ligand, CCL20, followed by T cell recruitment, renal tissue injury, albuminuria, and loss of renal function. CCR6 deficiency aggravated renal injury and increased mortality (from uremia) among nephritic mice. Compared with wild-type (WT) mice, CCR6 deficiency reduced infiltration of Tregs and Th17 cells but did not affect recruitment of Th1 cells in the setting of glomerulonephritis. Adoptive transfer of WT but not CCR6-deficient Tregs attenuated morphologic and functional renal injury in nephritic mice. Furthermore, reconstitution with WT Tregs protected CCR6-/- mice from aggravated nephritis. Taken together, these data suggest that CCR6 mediates renal recruitment of both Tregs and Th17 cells and that the reduction of anti-inflammatory Tregs in the presence of a fully functional Th1 response aggravates experimental glomerulonephritis.
AB - T cells recruited to the kidney contribute to tissue damage in crescentic and proliferative glomerulonephritides. Chemokines and their receptors regulate T cell trafficking, but the expression profile and functional importance of chemokine receptors for renal CD4+ T cell subsets are incompletely understood. In this study, we observed that renal FoxP3+CD4+ regulatory T cells (Tregs) and IL-17-producing CD4+ T (Th17) cells express the chemokine receptor CCR6, whereas IFNgamma-producing Th1 cells are CCR6-. Induction of experimental glomerulonephritis (nephrotoxic nephritis) in mice resulted in upregulation of the only CCR6 ligand, CCL20, followed by T cell recruitment, renal tissue injury, albuminuria, and loss of renal function. CCR6 deficiency aggravated renal injury and increased mortality (from uremia) among nephritic mice. Compared with wild-type (WT) mice, CCR6 deficiency reduced infiltration of Tregs and Th17 cells but did not affect recruitment of Th1 cells in the setting of glomerulonephritis. Adoptive transfer of WT but not CCR6-deficient Tregs attenuated morphologic and functional renal injury in nephritic mice. Furthermore, reconstitution with WT Tregs protected CCR6-/- mice from aggravated nephritis. Taken together, these data suggest that CCR6 mediates renal recruitment of both Tregs and Th17 cells and that the reduction of anti-inflammatory Tregs in the presence of a fully functional Th1 response aggravates experimental glomerulonephritis.
M3 - SCORING: Zeitschriftenaufsatz
VL - 21
SP - 974
EP - 985
JO - J AM SOC NEPHROL
JF - J AM SOC NEPHROL
SN - 1046-6673
IS - 6
M1 - 6
ER -