MicroRNA-155 drives TH17 immune response and tissue injury in experimental crescentic GN
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MicroRNA-155 drives TH17 immune response and tissue injury in experimental crescentic GN. / Krebs, Christian F; Kapffer, Sonja; Paust, Hans-Joachim; Schmidt, Tilman; Bennstein, Sabrina B; Peters, Anett; Stege, Gesa; Brix, Silke R; Meyer-Schwesinger, Catherine; Müller, Roman-Ulrich; Turner, Jan Eric; Steinmetz, Oliver M; Wolf, Gunter; Stahl, Rolf A K; Panzer, Ulf.
In: J AM SOC NEPHROL, Vol. 24, No. 12, 01.12.2013, p. 1955-65.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - MicroRNA-155 drives TH17 immune response and tissue injury in experimental crescentic GN
AU - Krebs, Christian F
AU - Kapffer, Sonja
AU - Paust, Hans-Joachim
AU - Schmidt, Tilman
AU - Bennstein, Sabrina B
AU - Peters, Anett
AU - Stege, Gesa
AU - Brix, Silke R
AU - Meyer-Schwesinger, Catherine
AU - Müller, Roman-Ulrich
AU - Turner, Jan Eric
AU - Steinmetz, Oliver M
AU - Wolf, Gunter
AU - Stahl, Rolf A K
AU - Panzer, Ulf
PY - 2013/12/1
Y1 - 2013/12/1
N2 - CD4(+) T cells play a pivotal role in the pathogenesis of autoimmune disease, including human and experimental crescentic GN. Micro-RNAs (miRs) have emerged as important regulators of immune cell development, but the impact of miRs on the regulation of the CD4(+) T cell immune response remains to be fully clarified. Here, we report that miR-155 expression is upregulated in the kidneys of patients with ANCA-associated crescentic GN and a murine model of crescentic GN (nephrotoxic nephritis). To elucidate the potential role of miR-155 in T cell-mediated inflammation, nephritis was induced in miR-155(-/-) and wild-type mice. The systemic and renal nephritogenic TH17 immune response decreased markedly in nephritic miR-155(-/-) mice. Consistent with this finding, miR-155-deficient mice developed less severe nephritis, with reduced histologic and functional injury. Adoptive transfer of miR-155(-/-) and wild-type CD4(+) T cells into nephritic recombination activating gene 1-deficient (Rag-1(-/-)) mice showed the T cell-intrinsic importance of miR-155 for the stability of pathogenic TH17 immunity. These findings indicate that miR-155 drives the TH17 immune response and tissue injury in experimental crescentic GN and show that miR-155 is a potential therapeutic target in TH17-mediated diseases.
AB - CD4(+) T cells play a pivotal role in the pathogenesis of autoimmune disease, including human and experimental crescentic GN. Micro-RNAs (miRs) have emerged as important regulators of immune cell development, but the impact of miRs on the regulation of the CD4(+) T cell immune response remains to be fully clarified. Here, we report that miR-155 expression is upregulated in the kidneys of patients with ANCA-associated crescentic GN and a murine model of crescentic GN (nephrotoxic nephritis). To elucidate the potential role of miR-155 in T cell-mediated inflammation, nephritis was induced in miR-155(-/-) and wild-type mice. The systemic and renal nephritogenic TH17 immune response decreased markedly in nephritic miR-155(-/-) mice. Consistent with this finding, miR-155-deficient mice developed less severe nephritis, with reduced histologic and functional injury. Adoptive transfer of miR-155(-/-) and wild-type CD4(+) T cells into nephritic recombination activating gene 1-deficient (Rag-1(-/-)) mice showed the T cell-intrinsic importance of miR-155 for the stability of pathogenic TH17 immunity. These findings indicate that miR-155 drives the TH17 immune response and tissue injury in experimental crescentic GN and show that miR-155 is a potential therapeutic target in TH17-mediated diseases.
KW - Animals
KW - Cells, Cultured
KW - Disease Models, Animal
KW - Glomerulonephritis
KW - Humans
KW - Immunity, Humoral
KW - Immunophenotyping
KW - Male
KW - Mice
KW - Mice, Congenic
KW - Mice, Inbred C57BL
KW - Mice, Mutant Strains
KW - MicroRNAs
KW - Neutrophils
KW - Spleen
KW - Th17 Cells
U2 - 10.1681/ASN.2013020130
DO - 10.1681/ASN.2013020130
M3 - SCORING: Journal article
C2 - 23949802
VL - 24
SP - 1955
EP - 1965
JO - J AM SOC NEPHROL
JF - J AM SOC NEPHROL
SN - 1046-6673
IS - 12
ER -