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Effector CD8(+) T cell-derived interleukin-10 enhances acute liver immunopathology
BACKGROUND & AIMS: Besides secreting pro-inflammatory cytokines, chemokines and effector molecules, effector CD8(+) T cells that arise upon acute infection with certain viruses have been shown to produce the regulatory cytokine interleukin (IL)-10 and, therefore, contain immunopathology. Whether...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
European Association for the Study of the Liver. Published by Elsevier B.V.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127652/ https://www.ncbi.nlm.nih.gov/pubmed/28483675 http://dx.doi.org/10.1016/j.jhep.2017.04.020 |
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author | Fioravanti, Jessica Di Lucia, Pietro Magini, Diletta Moalli, Federica Boni, Carolina Benechet, Alexandre Pierre Fumagalli, Valeria Inverso, Donato Vecchi, Andrea Fiocchi, Amleto Wieland, Stefan Purcell, Robert Ferrari, Carlo Chisari, Francis V. Guidotti, Luca G. Iannacone, Matteo |
author_facet | Fioravanti, Jessica Di Lucia, Pietro Magini, Diletta Moalli, Federica Boni, Carolina Benechet, Alexandre Pierre Fumagalli, Valeria Inverso, Donato Vecchi, Andrea Fiocchi, Amleto Wieland, Stefan Purcell, Robert Ferrari, Carlo Chisari, Francis V. Guidotti, Luca G. Iannacone, Matteo |
author_sort | Fioravanti, Jessica |
collection | PubMed |
description | BACKGROUND & AIMS: Besides secreting pro-inflammatory cytokines, chemokines and effector molecules, effector CD8(+) T cells that arise upon acute infection with certain viruses have been shown to produce the regulatory cytokine interleukin (IL)-10 and, therefore, contain immunopathology. Whether the same occurs during acute hepatitis B virus (HBV) infection and role that IL-10 might play in liver disease is currently unknown. METHODS: Mouse models of acute HBV pathogenesis, as well as chimpanzees and patients acutely infected with HBV, were used to analyse the role of CD8(+) T cell-derived IL-10 in liver immunopathology. RESULTS: Mouse HBV-specific effector CD8(+) T cells produce significant amounts of IL-10 upon in vivo antigen encounter. This is corroborated by longitudinal data in a chimpanzee acutely infected with HBV, where serum IL-10 was readily detectable and correlated with intrahepatic CD8(+) T cell infiltration and liver disease severity. Unexpectedly, mouse and human CD8(+) T cell-derived IL-10 was found to act in an autocrine/paracrine fashion to enhance IL-2 responsiveness, thus preventing antigen-induced HBV-specific effector CD8(+) T cell apoptosis. Accordingly, the use of mouse models of HBV pathogenesis revealed that the IL-10 produced by effector CD8(+) T cells promoted their own intrahepatic survival and, thus supported, rather than suppressed liver immunopathology. CONCLUSION: Effector CD8(+) T cell-derived IL-10 enhances acute liver immunopathology. Altogether, these results extend our understanding of the cell- and tissue-specific role that IL-10 exerts in immune regulation. Lay summary: Interleukin-10 is mostly regarded as an immunosuppressive cytokine. We show here that HBV-specific CD8(+) T cells produce IL-10 upon antigen recognition and that this cytokine enhances CD8(+) T cell survival. As such, IL-10 paradoxically promotes rather than suppresses liver disease. |
format | Online Article Text |
id | pubmed-7127652 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | European Association for the Study of the Liver. Published by Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71276522020-04-08 Effector CD8(+) T cell-derived interleukin-10 enhances acute liver immunopathology Fioravanti, Jessica Di Lucia, Pietro Magini, Diletta Moalli, Federica Boni, Carolina Benechet, Alexandre Pierre Fumagalli, Valeria Inverso, Donato Vecchi, Andrea Fiocchi, Amleto Wieland, Stefan Purcell, Robert Ferrari, Carlo Chisari, Francis V. Guidotti, Luca G. Iannacone, Matteo J Hepatol Research Article BACKGROUND & AIMS: Besides secreting pro-inflammatory cytokines, chemokines and effector molecules, effector CD8(+) T cells that arise upon acute infection with certain viruses have been shown to produce the regulatory cytokine interleukin (IL)-10 and, therefore, contain immunopathology. Whether the same occurs during acute hepatitis B virus (HBV) infection and role that IL-10 might play in liver disease is currently unknown. METHODS: Mouse models of acute HBV pathogenesis, as well as chimpanzees and patients acutely infected with HBV, were used to analyse the role of CD8(+) T cell-derived IL-10 in liver immunopathology. RESULTS: Mouse HBV-specific effector CD8(+) T cells produce significant amounts of IL-10 upon in vivo antigen encounter. This is corroborated by longitudinal data in a chimpanzee acutely infected with HBV, where serum IL-10 was readily detectable and correlated with intrahepatic CD8(+) T cell infiltration and liver disease severity. Unexpectedly, mouse and human CD8(+) T cell-derived IL-10 was found to act in an autocrine/paracrine fashion to enhance IL-2 responsiveness, thus preventing antigen-induced HBV-specific effector CD8(+) T cell apoptosis. Accordingly, the use of mouse models of HBV pathogenesis revealed that the IL-10 produced by effector CD8(+) T cells promoted their own intrahepatic survival and, thus supported, rather than suppressed liver immunopathology. CONCLUSION: Effector CD8(+) T cell-derived IL-10 enhances acute liver immunopathology. Altogether, these results extend our understanding of the cell- and tissue-specific role that IL-10 exerts in immune regulation. Lay summary: Interleukin-10 is mostly regarded as an immunosuppressive cytokine. We show here that HBV-specific CD8(+) T cells produce IL-10 upon antigen recognition and that this cytokine enhances CD8(+) T cell survival. As such, IL-10 paradoxically promotes rather than suppresses liver disease. European Association for the Study of the Liver. Published by Elsevier B.V. 2017-09 2017-05-05 /pmc/articles/PMC7127652/ /pubmed/28483675 http://dx.doi.org/10.1016/j.jhep.2017.04.020 Text en © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Research Article Fioravanti, Jessica Di Lucia, Pietro Magini, Diletta Moalli, Federica Boni, Carolina Benechet, Alexandre Pierre Fumagalli, Valeria Inverso, Donato Vecchi, Andrea Fiocchi, Amleto Wieland, Stefan Purcell, Robert Ferrari, Carlo Chisari, Francis V. Guidotti, Luca G. Iannacone, Matteo Effector CD8(+) T cell-derived interleukin-10 enhances acute liver immunopathology |
title | Effector CD8(+) T cell-derived interleukin-10 enhances acute liver immunopathology |
title_full | Effector CD8(+) T cell-derived interleukin-10 enhances acute liver immunopathology |
title_fullStr | Effector CD8(+) T cell-derived interleukin-10 enhances acute liver immunopathology |
title_full_unstemmed | Effector CD8(+) T cell-derived interleukin-10 enhances acute liver immunopathology |
title_short | Effector CD8(+) T cell-derived interleukin-10 enhances acute liver immunopathology |
title_sort | effector cd8(+) t cell-derived interleukin-10 enhances acute liver immunopathology |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127652/ https://www.ncbi.nlm.nih.gov/pubmed/28483675 http://dx.doi.org/10.1016/j.jhep.2017.04.020 |
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