IL-33 promotes GATA-3 polarization of gut-derived T cells in experimental and ulcerative colitis.

Abstract

BACKGROUND:

In the respiratory mucosa, interleukin (IL)-33, has been shown to enhance T helper 2 (TH2)-type responses through the master regulatory gene GATA-3. IL-33 is upregulated in ulcerative colitis (UC), and the aim was to assess if IL-33 holds a similar key position in the shaping of the immune response in experimental colitis (piroxicam-accelerated colitis (PAC) in IL-10 (-/-) mice, dextran sodium sulfate (DSS) model) and UC.

METHODS:

Colonic IL-33 expression was determined in UC (8 active UC, 8 quiescent UC, and 7 controls) and experimental colitis. Mesenteric lymph node (MesLN) T cells were isolated from PAC IL-10 (-/-) mice and stimulated with IL-33.

RESULTS:

The colonic IL-33 expression was significantly upregulated all forms of colitis (P < 0.01) and correlated with disease severity score and inflammation (P < 0.001), and with GATA-3 expression levels (P < 0.01); no correlation with the TH1-specific T-bet expression was observed. MesLN T cells stimulated with IL-33 had increased GATA-3 expression, and showed an IL-33 dose-dependent increase in secreted TH2-type cytokines, whereas this effect was abolished by blocking IL-33 signaling. The non-TH2-type cytokine IL-17 was upregulated by IL-33 but in a T cell receptor dependent manner, as opposed to TH2-type cytokines, which required only IL-33 stimulation.

CONCLUSIONS:

The study demonstrates that intestinal IL-33 is capable of inducing GATA-3 in mucosal T cells, and suggests that IL-33 is a key mediator of pathological TH2 and non-TH2-type responses in intestinal inflammation. Blocking IL-33 signaling could be a feasible option in the treatment of UC.

• Authors: Jakob Benedict Seidelin, Mehmet Coskun, Peter Helding Kvist, Thomas Lindebo Holm, Kristine Holgersen, Ole Haagen Nielsen
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 50 Issue 2 Pg. 180-90 (Feb 2015) ISSN: 1435-5922 [Electronic] Japan
• PMID: 25112700 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• GATA3 Transcription Factor
• GATA3 protein, human
• Gata3 protein, mouse
• IL33 protein, human
• Il33 protein, mouse
• Interleukin-33
• Interleukins
• Interleukin-10

Topics

• Adult
• Animals
• CD4-Positive T-Lymphocytes (immunology)
• Colitis, Ulcerative (immunology, pathology)
• Cytokines (metabolism)
• Disease Models, Animal
• Female
• GATA3 Transcription Factor (metabolism)
• Humans
• Immunity, Mucosal
• Interleukin-10 (genetics, immunology)
• Interleukin-33
• Interleukins (immunology, metabolism)
• Intestinal Mucosa (immunology)
• Mice, Inbred BALB C
• Mice, Knockout
• Middle Aged
• T-Lymphocyte Subsets (immunology)
• Th2 Cells
• Young Adult