IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn's disease

Kobayashi, T; Okamoto, S; Hisamatsu, T; Kamada, N; Chinen, H; Saito, R; Kitazume, M T; Nakazawa, A; Sugita, A; Koganei, K; Isobe, K; Hibi, T
December 2008
Gut;Dec2008, Vol. 57 Issue 12, p1682
Academic Journal
Background: A novel T helper (Th) cell lineage, Th17, that exclusively produces the proinflammatory cytokine interleukin 17 )1L17) has been reported to play important roles in various inflammatory diseases. 1L23 is also focused upon for its potential to promote 1h17. Here, the roles of the lL23/IL1 7 axis in inflammatory bowel diseases such as ulcerative colitis (UC) and Crohn's disease (CD) were investigated. Methods: Mucosal samples were obtained from surgically resected specimens (controls, n = 12; UC, n = 17; CD, n = 22). 1L17 production by isolated peripheral blood (PB) and lamina propria )LP) CD4~ cells was examined. Quantitative PCR amplification was performed to determine the mRNA expression levels of 1L17, interferon y (IFN'y), 1L23 receptor )1L23R) and retinoic acid-related orphan receptor -y (RORC) in LP CD4~ cells, and 1L12 family members, such as ILl 2p40, ILl 2p35 and lL23p19, in whole mucosal specimens. The effects of exogenous 1L23 on ILl 7 production by LP CD4~ cells were also examined. Results: 1L17 production was higher in LP CD4~ cells than in PB. Significant 1L17 mRNA upregulation in LP CD4~ cells was found in UC, while IFN-y was increased in CD. IL23R and RORC were upregulated in LP CD4~ cells isolated from both UC and CD. 1L17 production was significantly increased by 1L23 in LP CD4~ cells from UC but not CD. Upregulated lL23p19 mRNA expression was correlated with 1L17 in UC and IFN-y in CD. Conclusions: lL23 may play important roles in controlling the differential Thl/Thl 7 balance in both UC and CD, althouqh Th17 cells may exist in both diseases.


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