Immunohistochemical study of disease-specific immune reaction in inflammatory bowel disease.

炎症性肠病疾病特异性免疫反应的免疫组织化学研究。

• 批准号: 13670545
• 负责人: NAKAMURA Shiro
• 金额: $ 2.18万
• 依托单位: Osaka City University Graduate School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670545/
• 关键词: inflammatory bowel disease; ulcerative colitis; Crohn's disease; lymphocyte; B cell; plasma cell; prolifaration; immunohistochemistry; IBD(炎症性腸疾患); Ki67; basal plasmacytosis; plasmacytosis; 腸間膜リンパ節; 肉芽腫

We analyzed ulcerative colitis from the standpoint of lymphocytic expansion in the loco by immunohistochem- istry and flow cytometry. Ulcerative colitis was character- ized by a diffuse distribution of Ki-67+ small round cells particularly in the ulcer base (that were CD19+ and CD20-), with a significant number of them also CD138+. Immuno- electron microscopy for CD19 revealed an abundance of rough endoplasmic reticulum in the cytoplasm. These in- dicated that they are of immature plasma lineage cells. By contrast, plasma cells in Crohn's disease were negative for CD19, and the labeling for Ki-67 was infrequent, showing mature phenotype. Flow cytometry revealed an occurrence of CD19+ and CD20- cells in ulcerative colitis but not in Crohn's disease. The labeling index of Ki-67 among CD19+ plasma cells was positively correlated with the clinical activity of ulcerative colitis. High labeling of Ki-67 in CD19+ plasma cells is specific for active ulcerative colitis that was resistant to med … More ical treatment by corticosteroids.Next, We investigated he Th1 response and SLC and ELC in Crohn's disease pathogenesis immunohistochemicaly. ELC was almost undetectable in intestinal samples. SLC was found sporadically in lymphoid follicles, lymphoid aggregate venules, and lymphatic vessels. In mesenteric lymph nodes (MLNs), SLC was highly expressed in high endothelial venules (HEVs), lymphatic vessels, and stromal Dendritic cells (DCs), predominantly in T cell areas. ELC was highly expressed in mature DCs. There were significantly more SLC positive HEVs and ELC positive mature DCs, important components of T cell areas, in Crohn's disease. SLC, ELC, and CCR7 mRNA was significantly higher in Crohn's disease MLNs compared with Ulcerative colitis. Crohn's disease MLNs had increased expression of SLC and ELC, mainly in HEVs, mature DCs, and lymphatic vessels, inducing T cell hyperplasia. CCR7 mRNA was increased in T cell areas. The dominant Th1 immune response is facilitated by interaction of SLC positive HEVs/lymphatic vessels, ELC positive mature DCs, and CCR7 positive T cells in hyperplastic T cell areas. In Crohn's disease, memory T cells and mature DCs may home to MLN Less

我们采用免疫组织化学和流式细胞术从淋巴细胞扩张的角度分析溃疡性结肠炎。溃疡性结肠炎的特点是Ki-67+小圆细胞弥漫性分布，特别是在溃疡基底（CD19+和CD20-），其中也有相当数量的CD138+。CD19的免疫电镜显示细胞质中有丰富的粗糙内质网。这表明它们是未成熟的浆系细胞。相比之下，克罗恩病的浆细胞CD19阴性，Ki-67标记较少，表现为成熟表型。流式细胞术显示CD19+和CD20-细胞在溃疡性结肠炎中出现，而在克罗恩病中没有。CD19+浆细胞中Ki-67的标记指数与溃疡性结肠炎的临床活动呈正相关。CD19+浆细胞中Ki-67的高标记是对药物耐药的活动性溃疡性结肠炎的特异性。接下来，我们用免疫组化方法研究了Th1应答和SLC、ELC在克罗恩病发病机制中的作用。肠样品中几乎检测不到ELC。淋巴滤泡、淋巴聚集体小静脉和淋巴管零星可见SLC。在肠系膜淋巴结（mln）中，SLC在高内皮小静脉（HEVs）、淋巴管和基质树突状细胞（dc）中高度表达，主要在T细胞区表达。ELC在成熟的dc中高表达。在克罗恩病中，SLC阳性的hev和ELC阳性的成熟dc （T细胞区域的重要组成部分）明显更多。与溃疡性结肠炎相比，克罗恩病mln中SLC、ELC和CCR7 mRNA显著升高。克罗恩病mln中SLC和ELC表达增加，主要在hev、成熟dc和淋巴管中，诱导T细胞增生。T细胞区CCR7 mRNA表达升高。在增生性T细胞区，SLC阳性的hev /淋巴管、ELC阳性的成熟dc和CCR7阳性T细胞的相互作用促进了主导的Th1免疫应答。在克罗恩病中，记忆T细胞和成熟dc可能是MLN Less的宿主

项目成果

Oshitani N. et al.: "Decreased anti-Saccharomyces cerevisiae antibody titer by mesalazine in patients with Crohn's disease"J Gastroenterol Hepatol. 15. 1400-1403 (2001)

Oshitani N. 等人：“美沙拉秦可降低克罗恩病患者的抗酿酒酵母抗体滴度”J Gastroenterol Hepatol。

Augmented expression of secondary lymphoid tissue chemokine and EBI1 ligand chemokine in Crohn's disease

• DOI: 10.1136/jcp.2004.024828
• 发表时间: 2005-10-01
• 期刊: JOURNAL OF CLINICAL PATHOLOGY
• 影响因子: 3.4
• 作者: Kawashima, D;Oshitani, N;Arakawa, T
• 通讯作者: Arakawa, T

Oshitani N. et al.: "Heterogeneity of HPLC profiles of human class II MHC-bound peptides isolated from intestine with inflammatory bowel disease"Dig Dis Sci. Vol.47. 2088-2094 (2002)

Oshitani N. 等人：“从患有炎症性肠病的肠道中分离出的人 II 类 MHC 结合肽的 HPLC 谱的异质性”Dig Dis Sci。

Matsumoto T. et al.: "Role of granuloma in the immunopathogenesis of Crohn's disease"Digestion. 13-18 (2001)

Matsumoto T. 等人：“肉芽肿在克罗恩病免疫发病机制中的作用”消化。

rifiltration of CD19+plasma cells with frequent labeling of Ki-67 in corticosteroid-resistant activeulcerative colitis

皮质类固醇抵抗性活动性溃疡性结肠炎中频繁标记 Ki-67 的 CD19 浆细胞的再过滤

• 发表时间: 2006
• 期刊: Virchows Arch. 448
• 作者: Jinno Y;et al.
• 通讯作者: et al.