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...
Autores principales: | , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783311034312818688 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5879650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT stankokatarina cd96expressiondeterminestheinflammatorypotentialofil9producingth9cells AT iwertchristina cd96expressiondeterminestheinflammatorypotentialofil9producingth9cells AT appeltchristine cd96expressiondeterminestheinflammatorypotentialofil9producingth9cells AT vogtkatrin cd96expressiondeterminestheinflammatorypotentialofil9producingth9cells AT schumannjulia cd96expressiondeterminestheinflammatorypotentialofil9producingth9cells AT strunkfranziskajanina cd96expressiondeterminestheinflammatorypotentialofil9producingth9cells AT ahrlichstefanie cd96expressiondeterminestheinflammatorypotentialofil9producingth9cells AT schlickeiserstephan cd96expressiondeterminestheinflammatorypotentialofil9producingth9cells AT romagnanichiara cd96expressiondeterminestheinflammatorypotentialofil9producingth9cells AT jurchottkarsten cd96expressiondeterminestheinflammatorypotentialofil9producingth9cells AT meiselchristian cd96expressiondeterminestheinflammatorypotentialofil9producingth9cells AT willimskygerald cd96expressiondeterminestheinflammatorypotentialofil9producingth9cells AT kuhlanjaa cd96expressiondeterminestheinflammatorypotentialofil9producingth9cells AT sawitzkibirgit cd96expressiondeterminestheinflammatorypotentialofil9producingth9cells |