期刊
JOURNAL OF GASTROENTEROLOGY
卷 50, 期 2, 页码 180-190出版社
SPRINGER JAPAN KK
DOI: 10.1007/s00535-014-0982-7
关键词
Experimental colitis; GATA-3; Interleukin-33; T-bet; Ulcerative colitis
资金
- Fonden til Laegevidenskabens Fremme (the A. P. Moller Foundation)
- Novo Nordisk A/S
- Family Erichsen Memorial Foundation
- Lundbeck Foundation
- Axel Muusfeldts Foundation
- Foundation of Aase and Ejnar Danielsen
- Danish Council for Independent Research
In the respiratory mucosa, interleukin (IL)-33, has been shown to enhance T helper 2 (T(H)2)-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. 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. 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 T(H)1-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 T(H)2-type cytokines, whereas this effect was abolished by blocking IL-33 signaling. The non-T(H)2-type cytokine IL-17 was upregulated by IL-33 but in a T cell receptor dependent manner, as opposed to T(H)2-type cytokines, which required only IL-33 stimulation. 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 T(H)2 and non-T(H)2-type responses in intestinal inflammation. Blocking IL-33 signaling could be a feasible option in the treatment of UC.
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