Colonic lamina propria dendritic cells in mice with CD4+ T cell-induced colitis
Colonic lamina propria dendritic cells in mice with CD4+ T cell-induced colitis
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DOI：
10.1002/eji.200323518
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发表时间：
2003-04-01
影响因子：
5.4
通讯作者：
Reimann, J
中科院分区：
文献类型：
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作者：
Krajina, T;Leithäuser, F;Reimann, J
正常和免疫缺陷（RAG 1（-/-））C57 BL/6（136）小鼠结肠固有层（cLP）中的CD 11 c（+）（F4/80（-）CD 68（-））树突状细胞（DC）显示高表面表达MHC I/ II类分子和CD 1d，低表面表达CD 40、CD 80、CD 86共刺激分子。来自正常或IMHC II类缺陷B6小鼠的CD 4（+）α-T细胞转移到同源RAG 1-/-宿主中诱导进行性致死性结肠炎。随着结肠炎的发展，炎症cLP中的DC数量增加，并上调CD 1d、MHC II类分子和CD 40、CD 80、CD 86共刺激分子的表面表达。来自非移植（健康）和移植（患病）小鼠的cLP DC响应于CD 40信号传导产生相似量的IL-12 p70和IL-10，但是在患有结肠炎的小鼠中诱导的IL-12 p40释放比在非移植小鼠中高5-15倍。IL-12 p40与p19的结合产生IL-23。来自移植的患病小鼠的新鲜分离的cLP淋巴细胞（cLPL）比来自非移植的健康小鼠的cLPL表达多3-10倍的p19转录物。通过cLPL的p19表达响应于CD 40连接而进一步上调。来自患有结肠炎的移植小鼠（但不是来自非移植对照）的新鲜分离的cLIP DC刺激共培养的NKT细胞释放IFN-γ（但不是IL-4或IL-13）。在结肠炎中，DC在cLP中积累，显示活化的表面表型，上调IL-12 p40和p19表达，并“自发地”刺激NKT样细胞。cLP DC可能是原位调节粘膜T细胞应答的新治疗方法的感兴趣的靶标。
CD11c(+) (F4/80(-) CD68(-)) dendritic cells (DC) in the colonic lamina propria (cLP) of normal and immunodeficient (RAG1(-/-)) C57BL/6 (136) mice show high surface expression of MHC class I/ II molecules and CD1d, and low surface expression of CD40, CD80, CD86 costimulator molecules. CD4(+) aalphabeta T cells from normal or IMHC class II-deficient B6 mice transferred into congenic RAG1-/- hosts induce a progressive, lethal colitis. Concomitant with colitis development, DC in the inflamed cLP increase in number and up-regulate surface expression of CD1d, MHC class II molecules and CD40, CD80, CD86 costimulator molecules. cLP DC from non-transplanted (healthy) and transplanted (diseased) mice produce similar amounts of IL-12 p70 and IL-10 in response to CD40 signaling, but the inducible IL-12 p40 release is 5-15-fold higher in mice with colitis than in non-transplanted mice. Binding of IL-12 p40 to p19 generates IL-23. Freshly isolated cLP lymphocytes (cLPL) from transplanted, diseased mice express 3-10-fold more p19 transcripts than cLPL from non-transplanted, healthy mice. p19 expression by cLPL is further up-regulated in response to CD40 ligation. Freshly isolated cLIP DC from transplanted mice with colitis (but not from non-transplanted controls) stimulate IFN-gamma (but not IL-4 or IL-13) release by co-cultured NKT cells. In colitis, DC accumulate in the cLP, show an activated surface phenotype, up-regulate IL-12 p40 and p19 expression, and 'spontaneously' stimulate NKT-like cells. cLP DC may be interesting targets for novel therapeutic approaches to modulate mucosal T cell responses in situ.