Characterization of colonic and mesenteric lymph node dendritic cell subpopulations in a murine adoptive transfer model of inflammatory bowel disease
Characterization of colonic and mesenteric lymph node dendritic cell subpopulations in a murine adoptive transfer model of inflammatory bowel disease
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DOI：
10.1097/00054725-200411000-00018
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发表时间：
2004-11-01
影响因子：
4.9
通讯作者：
Flesch, IEA
中科院分区：
文献类型：
--
作者：
Karlis, J;Penttila, I;Flesch, IEA
溃疡性结肠炎和克罗恩病，统称为炎症性肠病（IBD），是肠道的慢性炎症性疾病，困扰着全世界超过400万人。肠道炎症的特征在于对肠道植物群中正常无害抗原的异常粘膜免疫应答。在克罗恩病中，致病性粘膜免疫应答是典型的T辅助（T（H）1）型细胞应答，而溃疡性结肠炎主要与T（H）2应答相关。我们对树突状细胞在导致T细胞活化和慢性肠道炎症的早期免疫事件中的作用感兴趣。使用IBD的小鼠过继转移模型，我们发现在IBD的早期阶段，在上皮病变和组织降解出现之前，树突状细胞在结肠和肠系膜淋巴结中积累。原位免疫染色和流式细胞术分析显示，大约50%的结肠树突状细胞是CD 11b（+）B220（-）髓样树突状细胞，50%表达CD 11b（-）B220（+）浆细胞样表型。在相应的肠系膜淋巴结，约16%的浆细胞样树突状细胞。结肠髓样树突状细胞显示表达共刺激分子CD 40。两者，结肠髓样和浆细胞样树突状细胞释放干扰素-α原位和刺激T细胞增殖离体。我们的研究结果表明，树突状细胞可以在肠道成熟，而不迁移到肠系膜淋巴结。成熟的肠道树突状细胞可形成局部T细胞反应的成核位点，并在IBD的发病机制中发挥重要作用。
Ulcerative colitis and Crohn's disease, collectively termed inflammatory bowel diseases (IBD), are chronic inflammatory diseases of the intestine that afflict more than 4 million people worldwide. Intestinal inflammation is characterized by an abnormal mucosal immune response to normally harmless antigens in the gut flora. In Crohn's disease, the pathogenic mucosal immune response is a typical T helper (T(H)1) type cell response, whereas ulcerative colitis is predominantly associated with a T(H)2 response. We are interested in the role of dendritic cells in early immunologic events leading to T cell activation and chronic intestinal inflammation. Using a murine adoptive transfer model of IBD, we found an accumulation of dendritic cells in colon and mesenteric lymph nodes during the early stage of IBD before the appearance of epithelial lesions and tissue degradation. In situ immunostaining and flow-cytometric analysis revealed that approximately 50% of colonic dendritic cells were CD11b(+) B220(-) myeloid dendritic cells and 50% expressed the CD11b(-) B220(+) plasmacytoid phenotype. In corresponding mesenteric lymph nodes, approximately 16% were plasmacytoid dendritic cells. Colonic myeloid dendritic cells were shown to express the co-stimulatory molecule CD40. Both, colonic myeloid and plasmacytoid dendritic cells released interferon-alpha in situ and stimulated T cell proliferation ex vivo. Our results show that dendritic cells can mature in the intestine without migrating to mesenteric lymph nodes. Mature intestinal dendritic cells may form a nucleation site for a local T cell response and play an important role in the pathogenesis of IBD.