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

Nat Immunol. 2014 Jul;15(7):676-86. doi: 10.1038/ni.2920. Epub 2014 Jun 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Claudin-2 / genetics
  • Colitis / etiology*
  • Colitis / immunology
  • Colitis, Ulcerative / immunology
  • Humans
  • Interleukin-9 / immunology
  • Intestinal Mucosa / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Proto-Oncogene Proteins / physiology*
  • Receptors, Interleukin-9 / physiology*
  • Signal Transduction / physiology*
  • T-Lymphocyte Subsets / physiology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Th2 Cells / immunology
  • Trans-Activators / physiology*
  • Wound Healing


  • Claudin-2
  • Interleukin-9
  • Proto-Oncogene Proteins
  • Receptors, Interleukin-9
  • Trans-Activators
  • proto-oncogene protein Spi-1