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Host dysbiosis negatively impacts IL-9-producing T-cell differentiation and antitumour immunity

BACKGROUND: Host–microbiota interactions shape T-cell differentiation and promote tumour immunity. Although IL-9-producing T cells have been described as potent antitumour effectors, their role in microbiota-mediated tumour control remains unclear. METHODS: We analysed the impact of the intestinal m...

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Autores principales: Almeida, Rafael Ribeiro, Vieira, Raquel de Souza, Castoldi, Angela, Terra, Fernanda Fernandes, Melo, Amanda Campelo L., Canesso, Maria Cecília Campos, Lemos, Luísa, Cipelli, Marcella, Rana, Nisha, Hiyane, Meire Ioshie, Pearce, Erika L., Martins, Flaviano dos Santos, Faria, Ana Maria Caetano de, Câmara, Niels Olsen Saraiva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434765/
https://www.ncbi.nlm.nih.gov/pubmed/32499569
http://dx.doi.org/10.1038/s41416-020-0915-6
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author Almeida, Rafael Ribeiro
Vieira, Raquel de Souza
Castoldi, Angela
Terra, Fernanda Fernandes
Melo, Amanda Campelo L.
Canesso, Maria Cecília Campos
Lemos, Luísa
Cipelli, Marcella
Rana, Nisha
Hiyane, Meire Ioshie
Pearce, Erika L.
Martins, Flaviano dos Santos
Faria, Ana Maria Caetano de
Câmara, Niels Olsen Saraiva
author_facet Almeida, Rafael Ribeiro
Vieira, Raquel de Souza
Castoldi, Angela
Terra, Fernanda Fernandes
Melo, Amanda Campelo L.
Canesso, Maria Cecília Campos
Lemos, Luísa
Cipelli, Marcella
Rana, Nisha
Hiyane, Meire Ioshie
Pearce, Erika L.
Martins, Flaviano dos Santos
Faria, Ana Maria Caetano de
Câmara, Niels Olsen Saraiva
author_sort Almeida, Rafael Ribeiro
collection PubMed
description BACKGROUND: Host–microbiota interactions shape T-cell differentiation and promote tumour immunity. Although IL-9-producing T cells have been described as potent antitumour effectors, their role in microbiota-mediated tumour control remains unclear. METHODS: We analysed the impact of the intestinal microbiota on the differentiation of colonic lamina propria IL-9-producing T cells in germ-free and dysbiotic mice. Systemic effects of the intestinal microbiota on IL-9-producing T cells and the antitumour role of IL-9 were analysed in a model of melanoma-challenged dysbiotic mice. RESULTS: We show that germ-free mice have lower frequency of colonic lamina propria IL-9-producing T cells when compared with conventional mice, and that intestinal microbiota reconstitution restores cell frequencies. Long-term antibiotic treatment promotes host dysbiosis, diminishes intestinal IL-4 and TGF-β gene expression, decreases the frequency of colonic lamina propria IL-9-producing T cells, increases the susceptibility to tumour development and reduces the frequency of IL-9-producing T cells in the tumour microenvironment. Faecal transplant restores intestinal microbiota diversity, and the frequency of IL-9-producing T cells in the lungs of dysbiotic animals, restraining tumour burden. Finally, recombinant IL-9 injection enhances tumour control in dysbiotic mice. CONCLUSIONS: Host–microbiota interactions are required for adequate differentiation and antitumour function of IL-9-producing T cells.
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spelling pubmed-74347652021-06-05 Host dysbiosis negatively impacts IL-9-producing T-cell differentiation and antitumour immunity Almeida, Rafael Ribeiro Vieira, Raquel de Souza Castoldi, Angela Terra, Fernanda Fernandes Melo, Amanda Campelo L. Canesso, Maria Cecília Campos Lemos, Luísa Cipelli, Marcella Rana, Nisha Hiyane, Meire Ioshie Pearce, Erika L. Martins, Flaviano dos Santos Faria, Ana Maria Caetano de Câmara, Niels Olsen Saraiva Br J Cancer Article BACKGROUND: Host–microbiota interactions shape T-cell differentiation and promote tumour immunity. Although IL-9-producing T cells have been described as potent antitumour effectors, their role in microbiota-mediated tumour control remains unclear. METHODS: We analysed the impact of the intestinal microbiota on the differentiation of colonic lamina propria IL-9-producing T cells in germ-free and dysbiotic mice. Systemic effects of the intestinal microbiota on IL-9-producing T cells and the antitumour role of IL-9 were analysed in a model of melanoma-challenged dysbiotic mice. RESULTS: We show that germ-free mice have lower frequency of colonic lamina propria IL-9-producing T cells when compared with conventional mice, and that intestinal microbiota reconstitution restores cell frequencies. Long-term antibiotic treatment promotes host dysbiosis, diminishes intestinal IL-4 and TGF-β gene expression, decreases the frequency of colonic lamina propria IL-9-producing T cells, increases the susceptibility to tumour development and reduces the frequency of IL-9-producing T cells in the tumour microenvironment. Faecal transplant restores intestinal microbiota diversity, and the frequency of IL-9-producing T cells in the lungs of dysbiotic animals, restraining tumour burden. Finally, recombinant IL-9 injection enhances tumour control in dysbiotic mice. CONCLUSIONS: Host–microbiota interactions are required for adequate differentiation and antitumour function of IL-9-producing T cells. Nature Publishing Group UK 2020-06-05 2020-08-18 /pmc/articles/PMC7434765/ /pubmed/32499569 http://dx.doi.org/10.1038/s41416-020-0915-6 Text en © The Author(s), under exclusive licence to Cancer Research UK 2020 https://creativecommons.org/licenses/by/4.0/Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
spellingShingle Article
Almeida, Rafael Ribeiro
Vieira, Raquel de Souza
Castoldi, Angela
Terra, Fernanda Fernandes
Melo, Amanda Campelo L.
Canesso, Maria Cecília Campos
Lemos, Luísa
Cipelli, Marcella
Rana, Nisha
Hiyane, Meire Ioshie
Pearce, Erika L.
Martins, Flaviano dos Santos
Faria, Ana Maria Caetano de
Câmara, Niels Olsen Saraiva
Host dysbiosis negatively impacts IL-9-producing T-cell differentiation and antitumour immunity
title Host dysbiosis negatively impacts IL-9-producing T-cell differentiation and antitumour immunity
title_full Host dysbiosis negatively impacts IL-9-producing T-cell differentiation and antitumour immunity
title_fullStr Host dysbiosis negatively impacts IL-9-producing T-cell differentiation and antitumour immunity
title_full_unstemmed Host dysbiosis negatively impacts IL-9-producing T-cell differentiation and antitumour immunity
title_short Host dysbiosis negatively impacts IL-9-producing T-cell differentiation and antitumour immunity
title_sort host dysbiosis negatively impacts il-9-producing t-cell differentiation and antitumour immunity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434765/
https://www.ncbi.nlm.nih.gov/pubmed/32499569
http://dx.doi.org/10.1038/s41416-020-0915-6
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