Role of appendix in the development of inflammatory bowel disease in TCR-alpha mutant mice
Role of appendix in the development of inflammatory bowel disease in TCR-alpha mutant mice
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DOI：
10.1084/jem.184.2.707
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发表时间：
1996-08-01
影响因子：
15.3
通讯作者：
Bhan, AK
中科院分区：
文献类型：
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作者：
Mizoguchi, A;Mizoguchi, E;Bhan, AK
T细胞受体-α突变小鼠（TCR-α（-/-）），通过基因靶向胚胎干细胞中的TCR-α基因创建，自发发展类似于人类溃疡性结肠炎的炎症性肠病（IBD）。由于肠道相关淋巴样组织可能在慢性肠道炎症的发展中起重要作用，我们检查了这些小鼠的阑尾淋巴滤泡（ALF）和派尔集合淋巴结（PP）的变化。我们发现ALF的结构与小肠内PP的结构非常相似;在这两种情况下，都发现了被表面上皮覆盖的淋巴滤泡（圆顶形成）。在TCR-α（-/-）小鼠中，通过体内掺入5-溴-2 '脱氧尿苷估计的阑尾淋巴滤泡中的增殖量是PP的两倍多。ELISPOT分析显示，与TCR-α（+/-）对照小鼠相比，TCR-α（-/-）小鼠的ALF中伊加、IgG 1和IgG 2a分泌增加，但IgM分泌B细胞没有增加。此外，与PP相比，TCR-α（-/-）小鼠显示ALF中产生抗细胞骨架蛋白原肌球蛋白的自身抗体的B细胞增加。当TCR-α（-/-）小鼠在年幼时（3-5周）进行阑尾切除术时，6-7个月时肠系膜淋巴结细胞的数量明显少于假手术的TCR-α（-/-）小鼠。此外，在1个月龄时进行阑尾切除术抑制了IBD的发展，在6-7个月的观察期内，这些小鼠中只有3.3%发展为IBD。相比之下，与80%的对照组相似，包括假手术的TCR-α（-/-）小鼠，在此期间发生IBD。这些结果表明，ALF，而不是PP，是参与疾病过程的细胞的引发位点，并且在TCR-α（-/-）小鼠中IBD的发展中起重要作用。
T cell receptor-alpha mutant mice (TCR-alpha(-/-)), created by gene targeting of the TCR-alpha gene in embryonic stem cells, spontaneously develop inflammatory bowel disease (IBD) resembling human ulcerative colitis. Since gut-associated lymyhoid tissue is likely to play an important role in the development of chronic intestinal inflammation, we examined the changes in the appendix lymphoid follicle (ALF) and Peyer's patches (PP) ill these mice. We found the structure of the ALF to be remarkably similar to that of the PP ill the small intestine; in both instances, lymphoid follicles covered by surface epithelium (dome-formation) were found. The amount of proliferation in the lymphoid follicles of the appendix estimated by in vivo incorporation of 5-bromo-2'deoxyuridine was more than two times that of PP in TCR-alpha(-/-) mice. ELISPOT assay showed an increase or IgA, IgG1, and IgG2a, but not IgM-secreting B cells in ALF oi TCR alpha(-/-) mice compared to TCR-alpha(+/-) control mice. Furthermore, TCR-alpha(-/-) mice revealed an increase of autoantibody-producing B cells against the cytoskeletal protein tropomyosin in ALF as compared to PP. When TCR-alpha(-/-) mice underwent appendectomy at a young age (3-5 wk), the number of mesenteric lymph nodes cells at 6-7 mo were markedly less than in the sham-operated TCR-alpha(-/-) mice. Furthermore, appendectomy at 1 mo of age suppressed the development of IBD, with only 3.3% of these mice developing IBD in the 6-7-mo period of observation. In contrast, similar to 80% of controls, including the sham-operated TCR-alpha(-/-) mice, developed IBD during this period. These results suggest that ALF, rather than PP, is the priming site of cells involved in the disease process and plays all important role in the development of IBD in TCR-alpha(-/-) mice.