TH9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells

Gerlach K, Hwang Y, Nikolaev A, Atreya R, Dornhoff H, Steiner S, Lehr HA, Wirtz S, Waisinan A, Rosenbauer F, Mckenzie ANJ, Weigmann B, Neurath M, Vieth M (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Nature Immunology Nature Research

Publisher: Nature Publishing Group

Book Volume: 15

Pages Range: 676-86

Journal Issue: 7

DOI: 10.1038/ni.2920

Abstract

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.

Authors with CRIS profile

Katharina Gerlach Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Raja Atreya Professur für Translationale Immunforschung bei chronisch entzündlichen Darmerkrankungen Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Benno Weigmann Medizinische Fakultät Markus Neurath Lehrstuhl für Innere Medizin I (Medizin 1) Michael Vieth

Involved external institutions

Universitätsmedizin der Johannes Gutenberg-Universität Mainz DE Germany (DE) Westfälische Wilhelms-Universität (WWU) Münster DE Germany (DE) Klinikum Bayreuth DE Germany (DE)

How to cite

APA:

Gerlach, K., Hwang, Y., Nikolaev, A., Atreya, R., Dornhoff, H., Steiner, S.,... Vieth, M. (2014). TH9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells. Nature Immunology, 15(7), 676-86. https://doi.org/10.1038/ni.2920

MLA:

Gerlach, Katharina, et al. "TH9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells." Nature Immunology 15.7 (2014): 676-86.

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