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IL-27 signalling regulates glycolysis in Th1 cells to limit immunopathology during infection
Inflammation is critical for controlling pathogens, but also responsible for symptoms of infectious diseases. IL-27 is an important regulator of inflammation and can limit development of IFNγ-producing Tbet(+) CD4(+) T (Th1) cells. IL-27 is thought to do this by stimulating IL-10 production by CD4(+...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584222/ https://www.ncbi.nlm.nih.gov/pubmed/33049000 http://dx.doi.org/10.1371/journal.ppat.1008994 |
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author | Montes de Oca, Marcela de Labastida Rivera, Fabian Winterford, Clay Frame, Teija C. M. Ng, Susanna S. Amante, Fiona H. Edwards, Chelsea L. Bukali, Luzia Wang, Yulin Uzonna, Jude E. Kuns, Rachel D. Zhang, Ping Kabat, Agnieszka Klein Geltink, Ramon I. Pearce, Edward J. Hill, Geoffrey R. Engwerda, Christian R. |
author_facet | Montes de Oca, Marcela de Labastida Rivera, Fabian Winterford, Clay Frame, Teija C. M. Ng, Susanna S. Amante, Fiona H. Edwards, Chelsea L. Bukali, Luzia Wang, Yulin Uzonna, Jude E. Kuns, Rachel D. Zhang, Ping Kabat, Agnieszka Klein Geltink, Ramon I. Pearce, Edward J. Hill, Geoffrey R. Engwerda, Christian R. |
author_sort | Montes de Oca, Marcela |
collection | PubMed |
description | Inflammation is critical for controlling pathogens, but also responsible for symptoms of infectious diseases. IL-27 is an important regulator of inflammation and can limit development of IFNγ-producing Tbet(+) CD4(+) T (Th1) cells. IL-27 is thought to do this by stimulating IL-10 production by CD4(+) T cells, but the underlying mechanisms of these immunoregulatory pathways are not clear. Here we studied the role of IL-27 signalling in experimental visceral leishmaniasis (VL) caused by infection of C57BL/6 mice with the human pathogen Leishmania donovani. We found IL-27 signalling was critical for the development of IL-10-producing Th1 (Tr1) cells during infection. Furthermore, in the absence of IL-27 signalling, there was improved control of parasite growth, but accelerated splenic pathology characterised by the loss of marginal zone macrophages. Critically, we discovered that IL-27 signalling limited glycolysis in Th1 cells during infection that in turn attenuated inflammation. Furthermore, the modulation of glycolysis in the absence of IL-27 signalling restricted tissue pathology without compromising anti-parasitic immunity. Together, these findings identify a novel mechanism by which IL-27 mediates immune regulation during disease by regulating cellular metabolism. |
format | Online Article Text |
id | pubmed-7584222 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-75842222020-10-28 IL-27 signalling regulates glycolysis in Th1 cells to limit immunopathology during infection Montes de Oca, Marcela de Labastida Rivera, Fabian Winterford, Clay Frame, Teija C. M. Ng, Susanna S. Amante, Fiona H. Edwards, Chelsea L. Bukali, Luzia Wang, Yulin Uzonna, Jude E. Kuns, Rachel D. Zhang, Ping Kabat, Agnieszka Klein Geltink, Ramon I. Pearce, Edward J. Hill, Geoffrey R. Engwerda, Christian R. PLoS Pathog Research Article Inflammation is critical for controlling pathogens, but also responsible for symptoms of infectious diseases. IL-27 is an important regulator of inflammation and can limit development of IFNγ-producing Tbet(+) CD4(+) T (Th1) cells. IL-27 is thought to do this by stimulating IL-10 production by CD4(+) T cells, but the underlying mechanisms of these immunoregulatory pathways are not clear. Here we studied the role of IL-27 signalling in experimental visceral leishmaniasis (VL) caused by infection of C57BL/6 mice with the human pathogen Leishmania donovani. We found IL-27 signalling was critical for the development of IL-10-producing Th1 (Tr1) cells during infection. Furthermore, in the absence of IL-27 signalling, there was improved control of parasite growth, but accelerated splenic pathology characterised by the loss of marginal zone macrophages. Critically, we discovered that IL-27 signalling limited glycolysis in Th1 cells during infection that in turn attenuated inflammation. Furthermore, the modulation of glycolysis in the absence of IL-27 signalling restricted tissue pathology without compromising anti-parasitic immunity. Together, these findings identify a novel mechanism by which IL-27 mediates immune regulation during disease by regulating cellular metabolism. Public Library of Science 2020-10-13 /pmc/articles/PMC7584222/ /pubmed/33049000 http://dx.doi.org/10.1371/journal.ppat.1008994 Text en © 2020 Montes de Oca 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Montes de Oca, Marcela de Labastida Rivera, Fabian Winterford, Clay Frame, Teija C. M. Ng, Susanna S. Amante, Fiona H. Edwards, Chelsea L. Bukali, Luzia Wang, Yulin Uzonna, Jude E. Kuns, Rachel D. Zhang, Ping Kabat, Agnieszka Klein Geltink, Ramon I. Pearce, Edward J. Hill, Geoffrey R. Engwerda, Christian R. IL-27 signalling regulates glycolysis in Th1 cells to limit immunopathology during infection |
title | IL-27 signalling regulates glycolysis in Th1 cells to limit immunopathology during infection |
title_full | IL-27 signalling regulates glycolysis in Th1 cells to limit immunopathology during infection |
title_fullStr | IL-27 signalling regulates glycolysis in Th1 cells to limit immunopathology during infection |
title_full_unstemmed | IL-27 signalling regulates glycolysis in Th1 cells to limit immunopathology during infection |
title_short | IL-27 signalling regulates glycolysis in Th1 cells to limit immunopathology during infection |
title_sort | il-27 signalling regulates glycolysis in th1 cells to limit immunopathology during infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584222/ https://www.ncbi.nlm.nih.gov/pubmed/33049000 http://dx.doi.org/10.1371/journal.ppat.1008994 |
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