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Abstract：
BACKGROUND: It is challenging to distinguish intestinal tuberculosis from Crohn\'s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)-23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells.
OBJECTIVE: To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn\'s disease.
METHODS: We analysed 133 patients with intestinal tuberculosis, 128 with Crohn\'s disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1β rs1143627, TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry.
RESULTS: The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn\'s disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01).
CONCLUSIONS: High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.
OBJECTIVE: To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn\'s disease.
METHODS: We analysed 133 patients with intestinal tuberculosis, 128 with Crohn\'s disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1β rs1143627, TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry.
RESULTS: The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn\'s disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01).
CONCLUSIONS: High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.
摘要：
背景：由于流行病学的动态变化和相似的临床特征，将肠结核与克罗恩病区分开具有挑战性。最近的研究表明，白细胞介素（IL）-23/IL-17轴相关基因的多态性可能通过影响Th17细胞的分化而影响肠黏膜免疫。
目的：探讨IL-23/IL-17轴相关基因的特异性单核苷酸多态性（SNPs）及影响肠结核和克罗恩病易感性的可能途径。
方法：我们分析了133例肠结核患者，128患有克罗恩病，和500个正常对照。从石蜡包埋的样本或全血提取DNA。用TaqMan测定对IL23/Th17轴中的四个SNP(IL22rs2227473、IL1βrs1143627、TGFβrs4803455和IL17rs8193036)进行基因分型。采用双荧光素酶报告基因法检测不同基因型rs2227473的转录活性水平。免疫组化法检测IL-22R1在不同肠道疾病中的表达。
结果：rs2227473的A等位基因频率（P=0.030，比值比=0.60，95％置信区间：0.37-0.95）显示肠结核和健康对照组之间的异常分布。A等位基因的存在与较高的IL-22转录活性相关(P<0.05)。此外,IL-22R1在肠淋巴组织中表达,尤其是在肠结核的情况下，并在巨噬细胞衍生的朗汉斯巨细胞中高度表达。免疫组化结果显示,IL-22R1在克罗恩病和肠结核患者中的表达明显高于肠息肉和结肠癌患者(P<0.01)。
结论：IL-22高表达似乎是肠结核的保护因素。IL-22R1在朗汉斯巨细胞中表达,这表明IL-22/IL-22R1系统连接适应性和先天免疫。
目的：探讨IL-23/IL-17轴相关基因的特异性单核苷酸多态性（SNPs）及影响肠结核和克罗恩病易感性的可能途径。
方法：我们分析了133例肠结核患者，128患有克罗恩病，和500个正常对照。从石蜡包埋的样本或全血提取DNA。用TaqMan测定对IL23/Th17轴中的四个SNP(IL22rs2227473、IL1βrs1143627、TGFβrs4803455和IL17rs8193036)进行基因分型。采用双荧光素酶报告基因法检测不同基因型rs2227473的转录活性水平。免疫组化法检测IL-22R1在不同肠道疾病中的表达。
结果：rs2227473的A等位基因频率（P=0.030，比值比=0.60，95％置信区间：0.37-0.95）显示肠结核和健康对照组之间的异常分布。A等位基因的存在与较高的IL-22转录活性相关(P<0.05)。此外,IL-22R1在肠淋巴组织中表达,尤其是在肠结核的情况下，并在巨噬细胞衍生的朗汉斯巨细胞中高度表达。免疫组化结果显示,IL-22R1在克罗恩病和肠结核患者中的表达明显高于肠息肉和结肠癌患者(P<0.01)。
结论：IL-22高表达似乎是肠结核的保护因素。IL-22R1在朗汉斯巨细胞中表达,这表明IL-22/IL-22R1系统连接适应性和先天免疫。
