Regulatory T cells control the Th1 immune response in murine crescentic glomerulonephritis.
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Regulatory T cells control the Th1 immune response in murine crescentic glomerulonephritis. / Paust, Hans-Joachim; Ostmann, Annett; Erhardt, Annette; Turner, Jan Eric; Velden, Joachim; Mittrücker, Hans Willi; Sparwasser, Tim; Panzer, Ulf; Tiegs, Gisa.
in: KIDNEY INT, Jahrgang 80, Nr. 2, 2, 2011, S. 154-164.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Regulatory T cells control the Th1 immune response in murine crescentic glomerulonephritis.
AU - Paust, Hans-Joachim
AU - Ostmann, Annett
AU - Erhardt, Annette
AU - Turner, Jan Eric
AU - Velden, Joachim
AU - Mittrücker, Hans Willi
AU - Sparwasser, Tim
AU - Panzer, Ulf
AU - Tiegs, Gisa
PY - 2011
Y1 - 2011
N2 - Crescentic glomerulonephritis is mediated by inappropriate humoral and cellular immune responses toward self-antigens that may result from defects in central and peripheral tolerance. Evidence now suggests that regulatory T cells (Tregs) may be of pathophysiological importance in proliferative and crescentic forms of glomerulonephritis. To analyze the role of endogenous Tregs in a T cell-dependent glomerulonephritis model of nephrotoxic nephritis, we used 'depletion of regulatory T cell' (DEREG) mice that express the diphtheria toxin receptor under control of the FoxP3 (forkhead box P3) gene promoter. Toxin injection into these mice efficiently depleted renal and splenic FoxP3(+) Treg cells as determined by fluorescent-activated cell sorting (FACS) and immunohistochemical analyses. Treg depletion exacerbated systemic and renal interferon-? (IFN?) expression and increased recruitment of IFN?-producing Th1 cells into the kidney without an effect on the Th17 immune response. The enhanced Th1 response, following Treg cell depletion, was associated with an aggravated course of glomerulonephritis as measured by glomerular crescent formation. Thus, our results establish the functional importance of endogenous Tregs in the control of a significantly enhanced systemic and renal Th1 immune response in experimental glomerulonephritis.
AB - Crescentic glomerulonephritis is mediated by inappropriate humoral and cellular immune responses toward self-antigens that may result from defects in central and peripheral tolerance. Evidence now suggests that regulatory T cells (Tregs) may be of pathophysiological importance in proliferative and crescentic forms of glomerulonephritis. To analyze the role of endogenous Tregs in a T cell-dependent glomerulonephritis model of nephrotoxic nephritis, we used 'depletion of regulatory T cell' (DEREG) mice that express the diphtheria toxin receptor under control of the FoxP3 (forkhead box P3) gene promoter. Toxin injection into these mice efficiently depleted renal and splenic FoxP3(+) Treg cells as determined by fluorescent-activated cell sorting (FACS) and immunohistochemical analyses. Treg depletion exacerbated systemic and renal interferon-? (IFN?) expression and increased recruitment of IFN?-producing Th1 cells into the kidney without an effect on the Th17 immune response. The enhanced Th1 response, following Treg cell depletion, was associated with an aggravated course of glomerulonephritis as measured by glomerular crescent formation. Thus, our results establish the functional importance of endogenous Tregs in the control of a significantly enhanced systemic and renal Th1 immune response in experimental glomerulonephritis.
KW - Animals
KW - Disease Models, Animal
KW - Mice
KW - Chemotaxis
KW - Glomerulonephritis/immunology
KW - Immunity, Cellular/immunology
KW - Interferon-gamma/biosynthesis
KW - Kidney/immunology/pathology
KW - Lymphocyte Depletion
KW - T-Lymphocytes, Regulatory/immunology
KW - Th1 Cells/immunology
KW - Animals
KW - Disease Models, Animal
KW - Mice
KW - Chemotaxis
KW - Glomerulonephritis/immunology
KW - Immunity, Cellular/immunology
KW - Interferon-gamma/biosynthesis
KW - Kidney/immunology/pathology
KW - Lymphocyte Depletion
KW - T-Lymphocytes, Regulatory/immunology
KW - Th1 Cells/immunology
M3 - SCORING: Journal article
VL - 80
SP - 154
EP - 164
JO - KIDNEY INT
JF - KIDNEY INT
SN - 0085-2538
IS - 2
M1 - 2
ER -
