MicroRNA-155 drives TH17 immune response and tissue injury in experimental crescentic GN.
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.
III Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany;
Christian F
CF
Krebs
Sonja
S
Kapffer
Hans-Joachim
HJ
Paust
Tilman
T
Schmidt
Sabrina B
SB
Bennstein
Anett
A
Peters
Gesa
G
Stege
Silke R
SR
Brix
Catherine
C
Meyer-Schwesinger
Roman-Ulrich
RU
Müller
Jan-Eric
JE
Turner
Oliver M
OM
Steinmetz
Gunter
G
Wolf
Rolf A K
RA
Stahl
Ulf
U
Panzer
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*
C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse