CD96 expression determines the inflammatory potential of IL-9–producing Th9 cells

Recent findings demonstrated proinflammatory functions of interleukin (IL)-9–producing T helper type (Th) 9 cells in the pathogenesis of intestinal bowel diseases (IBDs). However, also antiinflammatory properties have been ascribed to Th9 cells, pointing to a functional heterogeneity. To dissect the...

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Autores principales: Stanko, Katarina, Iwert, Christina, Appelt, Christine, Vogt, Katrin, Schumann, Julia, Strunk, Franziska Janina, Ahrlich, Stefanie, Schlickeiser, Stephan, Romagnani, Chiara, Jürchott, Karsten, Meisel, Christian, Willimsky, Gerald, Kühl, Anja A., Sawitzki, Birgit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879650/
https://www.ncbi.nlm.nih.gov/pubmed/29531070
http://dx.doi.org/10.1073/pnas.1708329115
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author Stanko, Katarina
Iwert, Christina
Appelt, Christine
Vogt, Katrin
Schumann, Julia
Strunk, Franziska Janina
Ahrlich, Stefanie
Schlickeiser, Stephan
Romagnani, Chiara
Jürchott, Karsten
Meisel, Christian
Willimsky, Gerald
Kühl, Anja A.
Sawitzki, Birgit
author_facet Stanko, Katarina
Iwert, Christina
Appelt, Christine
Vogt, Katrin
Schumann, Julia
Strunk, Franziska Janina
Ahrlich, Stefanie
Schlickeiser, Stephan
Romagnani, Chiara
Jürchott, Karsten
Meisel, Christian
Willimsky, Gerald
Kühl, Anja A.
Sawitzki, Birgit
author_sort Stanko, Katarina
collection PubMed
description Recent findings demonstrated proinflammatory functions of interleukin (IL)-9–producing T helper type (Th) 9 cells in the pathogenesis of intestinal bowel diseases (IBDs). However, also antiinflammatory properties have been ascribed to Th9 cells, pointing to a functional heterogeneity. To dissect the specific expression pattern and, especially, diversity of murine antigen-specific Th9 cells, we applied single cell transcription profiling. Th9 cells displayed reduced expression of typical activation markers, such as Cd40 ligand and Cd96, whereas expression of Cd25 and Cd83 was increased compared with other Th subsets. Importantly, we identified two subsets of Th9 cells differing above all in their CD96 expression. The heterogeneous CD96 expression was specific for Th9 cells and not observed for other Th subtypes, such as Th1 cells. Lower CD96 expression was also observed in human IL-9(+) compared with IFN-γ(+) T cells. Although Il9 was highly transcribed by all Th9 cells, IL-9 mRNA and protein expression was increased in CD96(low) cells. Transfer of CD96(low) Th9 cells into recombination activating gene 1-deficient (Rag1(−/−)) mice caused severe weight loss, intestinal and colonic inflammation, and destruction of allogeneic skin grafts and thus showed high inflammatory potential. This was associated with their expansion and tissue accumulation. Contrastingly, CD96(high) Th9 cells did not cause colitis and showed reduced expansion and migratory potential. Blockade of CD96 completely restored the expansion and inflammatory properties of CD96(high) Th9 cells. Collectively, our data suggest an inhibitory role for the cosignaling receptor CD96 in Th9 cells, raising new opportunities in the treatment of IL-9–associated inflammations such as IBD.
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spelling pubmed-58796502018-04-03 CD96 expression determines the inflammatory potential of IL-9–producing Th9 cells Stanko, Katarina Iwert, Christina Appelt, Christine Vogt, Katrin Schumann, Julia Strunk, Franziska Janina Ahrlich, Stefanie Schlickeiser, Stephan Romagnani, Chiara Jürchott, Karsten Meisel, Christian Willimsky, Gerald Kühl, Anja A. Sawitzki, Birgit Proc Natl Acad Sci U S A PNAS Plus Recent findings demonstrated proinflammatory functions of interleukin (IL)-9–producing T helper type (Th) 9 cells in the pathogenesis of intestinal bowel diseases (IBDs). However, also antiinflammatory properties have been ascribed to Th9 cells, pointing to a functional heterogeneity. To dissect the specific expression pattern and, especially, diversity of murine antigen-specific Th9 cells, we applied single cell transcription profiling. Th9 cells displayed reduced expression of typical activation markers, such as Cd40 ligand and Cd96, whereas expression of Cd25 and Cd83 was increased compared with other Th subsets. Importantly, we identified two subsets of Th9 cells differing above all in their CD96 expression. The heterogeneous CD96 expression was specific for Th9 cells and not observed for other Th subtypes, such as Th1 cells. Lower CD96 expression was also observed in human IL-9(+) compared with IFN-γ(+) T cells. Although Il9 was highly transcribed by all Th9 cells, IL-9 mRNA and protein expression was increased in CD96(low) cells. Transfer of CD96(low) Th9 cells into recombination activating gene 1-deficient (Rag1(−/−)) mice caused severe weight loss, intestinal and colonic inflammation, and destruction of allogeneic skin grafts and thus showed high inflammatory potential. This was associated with their expansion and tissue accumulation. Contrastingly, CD96(high) Th9 cells did not cause colitis and showed reduced expansion and migratory potential. Blockade of CD96 completely restored the expansion and inflammatory properties of CD96(high) Th9 cells. Collectively, our data suggest an inhibitory role for the cosignaling receptor CD96 in Th9 cells, raising new opportunities in the treatment of IL-9–associated inflammations such as IBD. National Academy of Sciences 2018-03-27 2018-03-12 /pmc/articles/PMC5879650/ /pubmed/29531070 http://dx.doi.org/10.1073/pnas.1708329115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle PNAS Plus
Stanko, Katarina
Iwert, Christina
Appelt, Christine
Vogt, Katrin
Schumann, Julia
Strunk, Franziska Janina
Ahrlich, Stefanie
Schlickeiser, Stephan
Romagnani, Chiara
Jürchott, Karsten
Meisel, Christian
Willimsky, Gerald
Kühl, Anja A.
Sawitzki, Birgit
CD96 expression determines the inflammatory potential of IL-9–producing Th9 cells
title CD96 expression determines the inflammatory potential of IL-9–producing Th9 cells
title_full CD96 expression determines the inflammatory potential of IL-9–producing Th9 cells
title_fullStr CD96 expression determines the inflammatory potential of IL-9–producing Th9 cells
title_full_unstemmed CD96 expression determines the inflammatory potential of IL-9–producing Th9 cells
title_short CD96 expression determines the inflammatory potential of IL-9–producing Th9 cells
title_sort cd96 expression determines the inflammatory potential of il-9–producing th9 cells
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879650/
https://www.ncbi.nlm.nih.gov/pubmed/29531070
http://dx.doi.org/10.1073/pnas.1708329115
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