IL-27R-mediated regulation of IL-17 controls the development of respiratory syncytial virus-associated pathogenesis
Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved..
IL-27 is a heterodimeric cytokine composed of the subunits p28 and Epstein-Barr virus induced gene (EBI)-3 and is known for its effects on T-cell function and differentiation. IL-27 signals through the widely expressed IL-27 receptor (IL-27R), composed of the ligand-specific IL-27Rα chain and gp130. Engagement of the IL-27R activates STAT1 signaling, induces the expression of the type 1 helper T-cell (Th1) cytokine, interferon γ, and suppresses the differentiation of Th2 and Th17 cells. This study investigates the role of IL-27 signaling in respiratory syncytial virus (RSV) infection using IL-27Rα-deficient mice (IL-27rKO). Analysis of lungs from RSV-infected IL-27rKO mice showed exacerbation of mucus secretion compared with wild type, as well as enhanced expression of Muc5ac and Gob5 mRNA, markers of goblet cell metaplasia/hyperplasia. When compared with wild-type mice, RSV-challenged IL-27rKO mice had enhanced expression of Th17-associated cytokine IL-17a and an imbalance between Th1 and Th2 cytokine levels. Neutralization of IL-17 in RSV-infected IL-27rKO mice resulted in a significant decrease in the pulmonary mucus response and inhibition of the Th2-associated cytokines. Interestingly, IL-17 blockage led to an increase in the expression of IL-27 subunits p28 and EBI-3 in the lungs and lymph nodes of RSV-infected mice. Thus, IL-27 functions as a regulatory cytokine during RSV pathogenesis by suppressing the development of Th17 cells, but it also appears to be regulated by IL-17 induced by the virus.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:184 |
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| Enthalten in: |
The American journal of pathology - 184(2014), 6 vom: 13. Juni, Seite 1807-18 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
de Almeida Nagata, Denise E [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 30.12.2014 Date Revised 21.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ajpath.2014.02.004 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM237308819 |
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| 100 | 1 | |a de Almeida Nagata, Denise E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a IL-27R-mediated regulation of IL-17 controls the development of respiratory syncytial virus-associated pathogenesis |
| 264 | 1 | |c 2014 | |
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| 500 | |a Date Completed 30.12.2014 | ||
| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a IL-27 is a heterodimeric cytokine composed of the subunits p28 and Epstein-Barr virus induced gene (EBI)-3 and is known for its effects on T-cell function and differentiation. IL-27 signals through the widely expressed IL-27 receptor (IL-27R), composed of the ligand-specific IL-27Rα chain and gp130. Engagement of the IL-27R activates STAT1 signaling, induces the expression of the type 1 helper T-cell (Th1) cytokine, interferon γ, and suppresses the differentiation of Th2 and Th17 cells. This study investigates the role of IL-27 signaling in respiratory syncytial virus (RSV) infection using IL-27Rα-deficient mice (IL-27rKO). Analysis of lungs from RSV-infected IL-27rKO mice showed exacerbation of mucus secretion compared with wild type, as well as enhanced expression of Muc5ac and Gob5 mRNA, markers of goblet cell metaplasia/hyperplasia. When compared with wild-type mice, RSV-challenged IL-27rKO mice had enhanced expression of Th17-associated cytokine IL-17a and an imbalance between Th1 and Th2 cytokine levels. Neutralization of IL-17 in RSV-infected IL-27rKO mice resulted in a significant decrease in the pulmonary mucus response and inhibition of the Th2-associated cytokines. Interestingly, IL-17 blockage led to an increase in the expression of IL-27 subunits p28 and EBI-3 in the lungs and lymph nodes of RSV-infected mice. Thus, IL-27 functions as a regulatory cytokine during RSV pathogenesis by suppressing the development of Th17 cells, but it also appears to be regulated by IL-17 induced by the virus | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Chloride Channels |2 NLM | |
| 650 | 7 | |a Clca3a1 protein, mouse |2 NLM | |
| 650 | 7 | |a Ebi3 protein, mouse |2 NLM | |
| 650 | 7 | |a Il27 protein, mouse |2 NLM | |
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| 650 | 7 | |a Interleukin-17 |2 NLM | |
| 650 | 7 | |a Interleukins |2 NLM | |
| 650 | 7 | |a Minor Histocompatibility Antigens |2 NLM | |
| 650 | 7 | |a Muc5ac protein, mouse |2 NLM | |
| 650 | 7 | |a Mucin 5AC |2 NLM | |
| 650 | 7 | |a Mucoproteins |2 NLM | |
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| 650 | 7 | |a Receptors, Interleukin |2 NLM | |
| 650 | 7 | |a STAT1 Transcription Factor |2 NLM | |
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| 700 | 1 | |a Demoor, Tine |e verfasserin |4 aut | |
| 700 | 1 | |a Ptaschinski, Catherine |e verfasserin |4 aut | |
| 700 | 1 | |a Ting, Hung-An |e verfasserin |4 aut | |
| 700 | 1 | |a Jang, Sihyug |e verfasserin |4 aut | |
| 700 | 1 | |a Reed, Michelle |e verfasserin |4 aut | |
| 700 | 1 | |a Mukherjee, Sumanta |e verfasserin |4 aut | |
| 700 | 1 | |a Lukacs, Nicholas W |e verfasserin |4 aut | |
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