TH9 cells: new players in inflammatory bowel disease

▸ Gerlach K, Hwang Y, Nikolaev A, 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. Nat Immunol 2014;15:676–86.

T lymphocyte subsets play a critical role in the pathogenesis of IBD, but the relationship between T cell activation and epithelial cell damage in IBD remains to be elucidated. An increase in TH17 cell responses along with a decrease in regulatory T cell responses are associated with UC and Crohn's disease (CD); however, UC patients have a stronger TH2-related immune response, while CD patients have increased levels of TH1-related cytokines. In this study, the authors set out to investigate the role that TH9 cells play in the pathogenesis of IBD by characterising interleukin 9 (IL-9) expression in patients with IBD and in mouse models of acute and chronic colitis. TH9 cells, characterised by production of IL-9 and expression of the transcription factor PU.1, have been shown to contribute to parasitic infection and allergy. PU.1-expressing and IL-9-producing T cells were found in the gut mucosa of mainly UC patients, while cells that were targets of the IL-9 receptor (IL-9R) were located in the intestinal epithelium of UC and CD patients. In a mouse model of colitis induced by oxazolone, IL-9-producing TH9 cells were identified as key promoters of disease. Mice given anti-IL-9 or mice with PU.1 deficiency in T cells had reduced acute colitis. Using a novel IL-9 reporter mouse, the authors identified CD4 T cells as the principle source of IL-9. In oxazolone-induced colitis, IL-9 impaired barrier function and prevented wound healing. Together, this study demonstrates the critical role that IL-9-producing TH9 cells plays in the pathogenesis of IBD, particularly UC, by regulating intestinal barrier integrity and immunological function. From a clinical aspect, targeting IL-9 may be a …