Treg17 cells are programmed by Stat3 to suppress Th17 responses in systemic lupus
Copyright © 2015 International Society of Nephrology. Published by Elsevier Inc. All rights reserved..
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.
| Errataetall: |
CommentIn: Kidney Int. 2016 Jul;90(1):222-3. - PMID 27312447 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:89 |
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| Enthalten in: |
Kidney international - 89(2016), 1 vom: 15. Jan., Seite 158-66 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kluger, Malte A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.01.2017 Date Revised 10.01.2018 published: Print-Electronic CommentIn: Kidney Int. 2016 Jul;90(1):222-3. - PMID 27312447 Citation Status MEDLINE |
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| doi: |
10.1038/ki.2015.296 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM253677122 |
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| 520 | |a Copyright © 2015 International Society of Nephrology. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Luig, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Meyer, Matthias C |e verfasserin |4 aut | |
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| 700 | 1 | |a Meyer-Schwesinger, Catherine |e verfasserin |4 aut | |
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| 700 | 1 | |a Panzer, Ulf |e verfasserin |4 aut | |
| 700 | 1 | |a Steinmetz, Oliver M |e verfasserin |4 aut | |
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