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TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer

IL-22 has dual functions during tumorigenesis. Short term IL-22 production protects against genotoxic stress, whereas uncontrolled IL-22 activity promotes tumor growth; therefore, tight regulation of IL-22 is essential. TGF-β1 promotes the differentiation of Th17 cells, which are known to be a major...

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Autores principales: Perez, Laura Garcia, Kempski, Jan, M. McGee, Heather, Pelzcar, Penelope, Agalioti, Theodora, Giannou, Anastasios, Konczalla, Leonie, Brockmann, Leonie, Wahib, Ramez, Xu, Hao, Vesely, Maria Carolina Amezcua, Soukou, Shiwa, Steglich, Babett, Bedke, Tanja, Manthey, Carolin, Seiz, Oliver, Diercks, Björn-Philipp, Gnafakis, Stylianos, Guse, Andreas H., Perez, Daniel, Izbicki, Jakob R., Gagliani, Nicola, Flavell, Richard A., Huber, Samuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248087/
https://www.ncbi.nlm.nih.gov/pubmed/32451418
http://dx.doi.org/10.1038/s41467-020-16363-w
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author Perez, Laura Garcia
Kempski, Jan
M. McGee, Heather
Pelzcar, Penelope
Agalioti, Theodora
Giannou, Anastasios
Konczalla, Leonie
Brockmann, Leonie
Wahib, Ramez
Xu, Hao
Vesely, Maria Carolina Amezcua
Soukou, Shiwa
Steglich, Babett
Bedke, Tanja
Manthey, Carolin
Seiz, Oliver
Diercks, Björn-Philipp
Gnafakis, Stylianos
Guse, Andreas H.
Perez, Daniel
Izbicki, Jakob R.
Gagliani, Nicola
Flavell, Richard A.
Huber, Samuel
author_facet Perez, Laura Garcia
Kempski, Jan
M. McGee, Heather
Pelzcar, Penelope
Agalioti, Theodora
Giannou, Anastasios
Konczalla, Leonie
Brockmann, Leonie
Wahib, Ramez
Xu, Hao
Vesely, Maria Carolina Amezcua
Soukou, Shiwa
Steglich, Babett
Bedke, Tanja
Manthey, Carolin
Seiz, Oliver
Diercks, Björn-Philipp
Gnafakis, Stylianos
Guse, Andreas H.
Perez, Daniel
Izbicki, Jakob R.
Gagliani, Nicola
Flavell, Richard A.
Huber, Samuel
author_sort Perez, Laura Garcia
collection PubMed
description IL-22 has dual functions during tumorigenesis. Short term IL-22 production protects against genotoxic stress, whereas uncontrolled IL-22 activity promotes tumor growth; therefore, tight regulation of IL-22 is essential. TGF-β1 promotes the differentiation of Th17 cells, which are known to be a major source of IL-22, but the effect of TGF-β signaling on the production of IL-22 in CD4+ T cells is controversial. Here we show an increased presence of IL-17+IL-22+ cells and TGF-β1 in colorectal cancer compared to normal adjacent tissue, whereas the frequency of IL-22 single producing cells is not changed. Accordingly, TGF-β signaling in CD4+ T cells (specifically Th17 cells) promotes the emergence of IL-22-producing Th17 cells and thereby tumorigenesis in mice. IL-22 single producing T cells, however, are not dependent on TGF-β signaling. We show that TGF-β, via AhR induction, and PI3K signaling promotes IL-22 production in Th17 cells.
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spelling pubmed-72480872020-06-03 TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer Perez, Laura Garcia Kempski, Jan M. McGee, Heather Pelzcar, Penelope Agalioti, Theodora Giannou, Anastasios Konczalla, Leonie Brockmann, Leonie Wahib, Ramez Xu, Hao Vesely, Maria Carolina Amezcua Soukou, Shiwa Steglich, Babett Bedke, Tanja Manthey, Carolin Seiz, Oliver Diercks, Björn-Philipp Gnafakis, Stylianos Guse, Andreas H. Perez, Daniel Izbicki, Jakob R. Gagliani, Nicola Flavell, Richard A. Huber, Samuel Nat Commun Article IL-22 has dual functions during tumorigenesis. Short term IL-22 production protects against genotoxic stress, whereas uncontrolled IL-22 activity promotes tumor growth; therefore, tight regulation of IL-22 is essential. TGF-β1 promotes the differentiation of Th17 cells, which are known to be a major source of IL-22, but the effect of TGF-β signaling on the production of IL-22 in CD4+ T cells is controversial. Here we show an increased presence of IL-17+IL-22+ cells and TGF-β1 in colorectal cancer compared to normal adjacent tissue, whereas the frequency of IL-22 single producing cells is not changed. Accordingly, TGF-β signaling in CD4+ T cells (specifically Th17 cells) promotes the emergence of IL-22-producing Th17 cells and thereby tumorigenesis in mice. IL-22 single producing T cells, however, are not dependent on TGF-β signaling. We show that TGF-β, via AhR induction, and PI3K signaling promotes IL-22 production in Th17 cells. Nature Publishing Group UK 2020-05-25 /pmc/articles/PMC7248087/ /pubmed/32451418 http://dx.doi.org/10.1038/s41467-020-16363-w Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Perez, Laura Garcia
Kempski, Jan
M. McGee, Heather
Pelzcar, Penelope
Agalioti, Theodora
Giannou, Anastasios
Konczalla, Leonie
Brockmann, Leonie
Wahib, Ramez
Xu, Hao
Vesely, Maria Carolina Amezcua
Soukou, Shiwa
Steglich, Babett
Bedke, Tanja
Manthey, Carolin
Seiz, Oliver
Diercks, Björn-Philipp
Gnafakis, Stylianos
Guse, Andreas H.
Perez, Daniel
Izbicki, Jakob R.
Gagliani, Nicola
Flavell, Richard A.
Huber, Samuel
TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer
title TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer
title_full TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer
title_fullStr TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer
title_full_unstemmed TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer
title_short TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer
title_sort tgf-β signaling in th17 cells promotes il-22 production and colitis-associated colon cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248087/
https://www.ncbi.nlm.nih.gov/pubmed/32451418
http://dx.doi.org/10.1038/s41467-020-16363-w
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