title: Treg17 cells are programmed by Stat3 to suppress Th17 responses in systemic lupus.
abstract: Systemic lupus erythematosus (SLE) is a complex and potentially fatal autoimmune disorder. Although Th17 cells are thought to be central mediators of SLE, mechanisms underlying their counter regulation remain largely unknown. To help define this, we studied the function of the newly defined Stat3-dependent Th17-specific regulatory T cells (Treg17). Treg-specific deletion of Stat3 was achieved by generating Foxp3(Cre) × Stat3(fl/fl) mice and SLE was induced by intraperitoneal injection of pristane. Lack of Treg17 cells in these mice caused selectively enhanced peritoneal Th17 inflammation. Importantly, Treg17 deficiency also resulted in aggravated pulmonary vasculitis with increased percentages of Th17 cells and significantly higher mortality. Similarly, 4 and 9 months after pristane injection, analysis of renal and systemic immunity showed overshooting Th17 responses in the absence of Treg17 cells, associated with the aggravation of lupus nephritis. Expression of the Th17 characteristic trafficking receptor CCR6 was strikingly reduced on Tregs of Foxp3(Cre) × Stat3(fl/fl) mice, resulting in impaired renal Treg infiltration. Thus, Stat3-induced Treg17 cells are novel antiinflammatory mediators of SLE. One mechanism enabling Treg17 cells to target pathogenic Th17 responses is shared expression of the chemokine receptor CCR6.
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Eppendorf, Hamburg, Germany.
authors.forename: Malte A
authors.initials: MA
authors.lastname: Kluger
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Eppendorf, Hamburg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Melderis
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Eppendorf, Hamburg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Nosko
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Eppendorf, Hamburg, Germany.
authors.forename: Boeren
authors.initials: B
authors.lastname: Goerke
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Eppendorf, Hamburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Luig
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Eppendorf, Hamburg, Germany.
authors.forename: Matthias C
authors.initials: MC
authors.lastname: Meyer
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Eppendorf, Hamburg, Germany.
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Turner
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Eppendorf, Hamburg, Germany.
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyer-Schwesinger
authors.affiliation: Institut für Experimentelle Immunologie und Hepatologie, Universitätsklinikum Eppendorf, Hamburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Wegscheid
authors.affiliation: Institut für Experimentelle Immunologie und Hepatologie, Universitätsklinikum Eppendorf, Hamburg, Germany.
authors.forename: Gisa
authors.initials: G
authors.lastname: Tiegs
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Eppendorf, Hamburg, Germany.
authors.forename: Rolf A K
authors.initials: RA
authors.lastname: Stahl
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Eppendorf, Hamburg, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Eppendorf, Hamburg, Germany. Electronic address: o.steinmetz@uke.de.
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Steinmetz
mesh_terms: D000818:Animals; D005260:Female; D007136:Immunoglobulins / Q000097:blood; D007678:Kidney Glomerulus / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D008181:Lupus Nephritis / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D010538:Peritonitis / Q000276:immunology; D054399:Receptors, CCR6 / Q000032:analysis / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D013729:Terpenes; D058504:Th17 Cells / Q000737:chemistry / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology
chemical_list: C498126:CCR6 protein, mouse; D007136:Immunoglobulins; D054399:Receptors, CCR6; D050796:STAT3 Transcription Factor; D013729:Terpenes; C009042:pristane
keywords: autoimmunity; chemokine; glomerulonephritis; pristine