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
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Gut. 2008 Dec;57(12):1682-9. doi: 10.1136/gut.2007.135053. Epub 2008 Jul 24.
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.
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 (IFNgamma), 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.
IL17 production was higher in LP CD4(+) cells than in PB. Significant IL17 mRNA upregulation in LP CD4(+) cells was found in UC, while IFNgamma 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 IFNgamma in CD.
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.
据报道，一种专门产生促炎细胞因子白细胞介素17（IL17）的新型辅助性T（Th）细胞谱系——Th17，在多种炎症性疾病中发挥重要作用。IL23因其促进Th17的潜力也受到关注。在此，研究了IL23/IL17轴在溃疡性结肠炎（UC）和克罗恩病（CD）等炎症性肠病中的作用。
从手术切除标本中获取黏膜样本（对照组，n = 12；UC组，n = 17；CD组，n = 22）。检测分离的外周血（PB）和固有层（LP）CD4(+)细胞产生IL17的情况。进行定量PCR扩增以确定LP CD4(+)细胞中IL17、干扰素γ（IFNγ）、IL23受体（IL23R）和视黄酸相关孤儿受体γ（RORC）的mRNA表达水平，以及全黏膜标本中IL12家族成员如IL12p40、IL12p35和IL23p19的mRNA表达水平。还检测了外源性IL23对LP CD4(+)细胞产生IL17的影响。
LP CD4(+)细胞中IL17的产生高于PB。在UC中发现LP CD4(+)细胞中IL17 mRNA显著上调，而在CD中IFNγ增加。从UC和CD分离的LP CD4(+)细胞中IL23R和RORC上调。IL23使UC的LP CD4(+)细胞中IL17的产生显著增加，但对CD的LP CD4(+)细胞无此作用。上调的IL23p19 mRNA表达在UC中与IL17相关，在CD中与IFNγ相关。
尽管Th17细胞可能存在于UC和CD两种疾病中，但IL23可能在控制两者Th1/Th17的差异平衡中发挥重要作用。
