TH9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells
| Autor: | Andrew N. J. McKenzie, Stefanie Steiner, Ari Waisman, Heike Dornhoff, Benno Weigmann, Hans-Anton Lehr, Stefan Wirtz, Michael Vieth, Katharina Gerlach, YouYi Hwang, Raja Atreya, Alexej Nikolaev, Markus F. Neurath, Frank Rosenbauer |
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| Rok vydání: | 2013 |
| Předmět: |
T cell
Immunology Mice Th2 Cells T-Lymphocyte Subsets Proto-Oncogene Proteins medicine Immunology and Allergy Animals Humans Interleukin 9 Claudin-2 Colitis Intestinal Mucosa Receptor Transcription factor Receptors Interleukin-9 Mice Inbred BALB C Wound Healing biology business.industry Interleukin-9 T-Lymphocytes Helper-Inducer medicine.disease Ulcerative colitis medicine.anatomical_structure biology.protein Trans-Activators Colitis Ulcerative Antibody business Wound healing Signal Transduction |
| Zdroj: | Nature immunology. 15(7) |
| ISSN: | 1529-2916 |
| Popis: | The molecular checkpoints that drive inflammatory bowel diseases are incompletely understood. Here we found more T cells expressing the transcription factor PU.1 and interleukin 9 (IL-9) in patients with ulcerative colitis. In an animal model, citrine reporter mice had more IL-9-expressing mucosal T cells in experimental oxazolone-induced colitis. IL-9 deficiency suppressed acute and chronic colitis. Mice with PU.1 deficiency in T cells were protected from colitis, whereas treatment with antibody to IL-9 suppressed colitis. Functionally, IL-9 impaired intestinal barrier function and prevented mucosal wound healing in vivo. Thus, our findings suggest that the TH9 subset of helper T cells serves an important role in driving ulcerative colitis by regulating intestinal epithelial cells and that TH9 cells represent a likely target for the treatment of chronic intestinal inflammation. |
| Databáze: | OpenAIRE |
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