IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn's disease
IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn's disease
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DOI：
10.1136/gut.2007.135053
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发表时间：
2008-12-01
期刊：
影响因子：
24.5
通讯作者：
Hibi, T.
中科院分区：
文献类型：
--
作者：
Kobayashi, T.;Okamoto, S.;Hibi, T.
背景资料：一种新的辅助性T（Th）细胞系，Th 17，其专门产生促炎细胞因子白细胞介素17（IL 17），已被报道在各种炎性疾病中发挥重要作用。IL 23也因其促进Th 17的潜力而受到关注。在这里，IL 23/IL 17轴在炎症性肠病，如溃疡性结肠炎（UC）和克罗恩病（CD）的作用进行了调查。方法：粘液样品从手术切除标本（对照，n = 12; UC，n = 17; CD，n = 22）。检查了分离的外周血（PB）和固有层（LP）CD 4（+）细胞产生的IL 17。进行定量PCR扩增以确定LP CD 4（+）细胞中IL 17、干扰素γ（IFN γ）、IL 23受体（IL 23 R）和视黄酸相关孤儿受体γ（RORC）的mRNA表达水平，以及全粘膜标本中IL 12家族成员如IL 12 p40、IL 12 p35和IL 23 p19的mRNA表达水平。结果：LP CD 4（+）细胞产生IL 17的能力明显高于PB细胞。UC患者LP CD 4（+）细胞IL 17 mRNA表达显著上调，CD患者IFN γ表达显著上调。IL 23 R和RORC在分离自UC和CD的LP CD 4（+）细胞中上调。IL 23可显著增加UC LP CD 4（+）细胞中IL 17的产生，但对CD无影响。IL 23 p19 mRNA表达上调与UC中的IL 17和CD中的IFN γ相关。结论：IL 23可能在UC和CD中调节Th 1/Th 17的差异平衡中起重要作用，尽管Th 17细胞可能在两种疾病中都存在。
Background: A novel T helper (Th) cell lineage, Th17, that exclusively produces the proinflammatory cytokine interleukin 17 (IL17) has been reported to play important roles in various inflammatory diseases. IL23 is also focused upon for its potential to promote Th17. Here, the roles of the IL23/IL17 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). IL17 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 IL17, interferon gamma (IFN gamma), IL23 receptor (IL23R) and retinoic acid-related orphan receptor gamma (RORC) in LP CD4(+) cells, and IL12 family members, such as IL12p40, IL12p35 and IL23p19, in whole mucosal specimens. The effects of exogenous IL23 on IL17 production by LP CD4(+) cells were also examined.Results: IL17 production was higher in LP CD4(+) cells than in PB. Significant IL17 mRNA upregulation in LP CD4(+) cells was found in UC, while IFN gamma was increased in CD. IL23R and RORC were upregulated in LP CD4(+) cells isolated from both UC and CD. IL17 production was significantly increased by IL23 in LP CD4(+) cells from UC but not CD. Upregulated IL23p19 mRNA expression was correlated with IL17 in UC and IFN gamma in CD.Conclusions: IL23 may play important roles in controlling the differential Th1/Th17 balance in both UC and CD, although Th17 cells may exist in both diseases.