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IL-21R Signaling Suppresses IL-17(+) Gamma Delta T Cell Responses and Production of IL-17 Related Cytokines in the Lung at Steady State and After Influenza A Virus Infection
Influenza A virus (IAV) infection of the respiratory tract elicits a robust immune response, which is required for efficient virus clearance but at the same time can contribute to lung damage and enhanced morbidity. IL-21 is a member of the type I cytokine family and has many different immune-modula...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388622/ https://www.ncbi.nlm.nih.gov/pubmed/25849970 http://dx.doi.org/10.1371/journal.pone.0120169 |
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author | Moser, Emily K. Sun, Jie Kim, Taeg S. Braciale, Thomas J. |
author_facet | Moser, Emily K. Sun, Jie Kim, Taeg S. Braciale, Thomas J. |
author_sort | Moser, Emily K. |
collection | PubMed |
description | Influenza A virus (IAV) infection of the respiratory tract elicits a robust immune response, which is required for efficient virus clearance but at the same time can contribute to lung damage and enhanced morbidity. IL-21 is a member of the type I cytokine family and has many different immune-modulatory functions during acute and chronic virus infections, although its role in IAV infection has not been fully evaluated. In this report we evaluated the contributions of IL-21/IL-21 receptor (IL-21R) signaling to host defense in a mouse model of primary IAV infection using IL-21R knock out (KO) mice. We found that lack of IL-21R signaling had no significant impact on virus clearance, adaptive T cell responses, or myeloid cell accumulations in the respiratory tract. However, a subset of inflammatory cytokines were elevated in the bronchoalveolar lavage fluid of IL-21R KO mice, including IL-17. Although there was only a small increase in Th17 cells in the lungs of IL-21R KO mice, we observed a dramatic increase in gamma delta (γδ) T cells capable of producing IL-17 both after IAV infection and at steady state in the respiratory tract. Finally, we found that IL-21R signaling suppressed the accumulation of IL-17(+) γδ T cells in the respiratory tract intrinsically. Thus, our study reveals a previously unrecognized role of IL-21R signaling in regulating IL-17 production by γδ T cells. |
format | Online Article Text |
id | pubmed-4388622 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43886222015-04-21 IL-21R Signaling Suppresses IL-17(+) Gamma Delta T Cell Responses and Production of IL-17 Related Cytokines in the Lung at Steady State and After Influenza A Virus Infection Moser, Emily K. Sun, Jie Kim, Taeg S. Braciale, Thomas J. PLoS One Research Article Influenza A virus (IAV) infection of the respiratory tract elicits a robust immune response, which is required for efficient virus clearance but at the same time can contribute to lung damage and enhanced morbidity. IL-21 is a member of the type I cytokine family and has many different immune-modulatory functions during acute and chronic virus infections, although its role in IAV infection has not been fully evaluated. In this report we evaluated the contributions of IL-21/IL-21 receptor (IL-21R) signaling to host defense in a mouse model of primary IAV infection using IL-21R knock out (KO) mice. We found that lack of IL-21R signaling had no significant impact on virus clearance, adaptive T cell responses, or myeloid cell accumulations in the respiratory tract. However, a subset of inflammatory cytokines were elevated in the bronchoalveolar lavage fluid of IL-21R KO mice, including IL-17. Although there was only a small increase in Th17 cells in the lungs of IL-21R KO mice, we observed a dramatic increase in gamma delta (γδ) T cells capable of producing IL-17 both after IAV infection and at steady state in the respiratory tract. Finally, we found that IL-21R signaling suppressed the accumulation of IL-17(+) γδ T cells in the respiratory tract intrinsically. Thus, our study reveals a previously unrecognized role of IL-21R signaling in regulating IL-17 production by γδ T cells. Public Library of Science 2015-04-07 /pmc/articles/PMC4388622/ /pubmed/25849970 http://dx.doi.org/10.1371/journal.pone.0120169 Text en © 2015 Moser et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Moser, Emily K. Sun, Jie Kim, Taeg S. Braciale, Thomas J. IL-21R Signaling Suppresses IL-17(+) Gamma Delta T Cell Responses and Production of IL-17 Related Cytokines in the Lung at Steady State and After Influenza A Virus Infection |
title | IL-21R Signaling Suppresses IL-17(+) Gamma Delta T Cell Responses and Production of IL-17 Related Cytokines in the Lung at Steady State and After Influenza A Virus Infection |
title_full | IL-21R Signaling Suppresses IL-17(+) Gamma Delta T Cell Responses and Production of IL-17 Related Cytokines in the Lung at Steady State and After Influenza A Virus Infection |
title_fullStr | IL-21R Signaling Suppresses IL-17(+) Gamma Delta T Cell Responses and Production of IL-17 Related Cytokines in the Lung at Steady State and After Influenza A Virus Infection |
title_full_unstemmed | IL-21R Signaling Suppresses IL-17(+) Gamma Delta T Cell Responses and Production of IL-17 Related Cytokines in the Lung at Steady State and After Influenza A Virus Infection |
title_short | IL-21R Signaling Suppresses IL-17(+) Gamma Delta T Cell Responses and Production of IL-17 Related Cytokines in the Lung at Steady State and After Influenza A Virus Infection |
title_sort | il-21r signaling suppresses il-17(+) gamma delta t cell responses and production of il-17 related cytokines in the lung at steady state and after influenza a virus infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388622/ https://www.ncbi.nlm.nih.gov/pubmed/25849970 http://dx.doi.org/10.1371/journal.pone.0120169 |
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