Plasticity of Th17 Cells in Autoimmune Kidney Diseases.
The ability of CD4(+) T cells to differentiate into pathogenic Th1 and Th17 or protective T regulatory cells plays a pivotal role in the pathogenesis of autoimmune diseases. Recent data suggest that CD4(+) T cell subsets display a considerable plasticity. This plasticity seems to be a critical factor for their pathogenicity, but also for the potential transition of pathogenic effector T cells toward a more tolerogenic phenotype. The aim of the current study was to analyze the plasticity of Th17 cells in a mouse model of acute crescentic glomerulonephritis and in a mouse chronic model of lupus nephritis. By transferring in vitro generated, highly purified Th17 cells and by using IL-17A fate reporter mice, we demonstrate that Th17 cells fail to acquire substantial expression of the Th1 and Th2 signature cytokines IFN-γ and IL-13, respectively, or the T regulatory transcription factor Foxp3 throughout the course of renal inflammation. In an attempt to therapeutically break the stability of the Th17 phenotype in acute glomerulonephritis, we subjected nephritic mice to CD3-specific Ab treatment. Indeed, this treatment induced an immunoregulatory phenotype in Th17 cells, which was marked by high expression of IL-10 and attenuated renal tissue damage in acute glomerulonephritis. In summary, we show that Th17 cells display a minimum of plasticity in acute and chronic experimental glomerulonephritis and introduce anti-CD3 treatment as a tool to induce a regulatory phenotype in Th17 cells in the kidney that may be therapeutically exploited.
III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany; ckrebs@uke.de.
Christian F
CF
Krebs
III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany;
Jan-Eric
JE
Turner
III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany;
Hans-Joachim
HJ
Paust
III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany;
Sonja
S
Kapffer
III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany;
Tobias
0000-0002-8412-1840
T
Koyro
III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany;
Sonja
S
Krohn
Institute of Neuroimmunology and Multiple Sclerosis, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany;
Friederike
F
Ufer
Institute of Neuroimmunology and Multiple Sclerosis, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany;
Manuel A
MA
Friese
Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520;
Richard A
RA
Flavell
Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, London NW7 1AA, United Kingdom; and.
Brigitta
0000-0001-8781-336X
B
Stockinger
III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany;
Oliver M
OM
Steinmetz
III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany;
Rolf A K
0000-0002-6225-8600
RA
Stahl
I. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
Samuel
S
Huber
III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany;
Ulf
U
Panzer
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005921:Glomerulonephritis / Q000276:immunology*; D007150:Immunohistochemistry; D008181:Lupus Nephritis / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*