Department of Internal Medicine I, University of Regensburg, D-93053 Regensburg, Germany.
World J Gastroenterol. 2010 Jan 7;16(1):21-9. doi: 10.3748/wjg.v16.i1.21.
To investigate possible differences in dendritic cells (DC) within intestinal tissue of mice before and after induction of colitis.
Mucosal DC derived from intestinal tissue, as well as from mesenteric lymph nodes and spleen, were analyzed by fluorescence activated cell sorting (FACS) analysis. Supernatants of these cells were analyzed for secretion of different pro- and anti-inflammatory cytokines. Immunohistochemistry and immunofluorescence were performed on cryosections of mucosal tissue derived from animals with colitis as well as from healthy mice.
It was shown that DC derived from healthy intestinal lamina propria (LP) represented an immature phenotype as characterized by low-level expression of costimulatory cytokines. In contrast to DC from spleen and mesenteric lymph nodes (MLN) that secreted proinflammatory cytokines, LP-DC produced high levels of the anti-inflammatory cytokine IL-10. After induction of murine colitis in a CD4(+)CD62L(+) transfer model or in chronic dextran sulfate sodium-colitis, a marked increase of activated CD80(+) DC could be observed within the inflamed colonic tissue. Interestingly, in contrast to splenic DC, a significant population of DC within MLN and colonic LP expressed the mucosal integrin CD103 which was lost during colitis.
The constitutive secretion of anti-inflammatory cytokines by immature DC within the intestinal LP might regulate the homeostatic balance between mucosal immunity and tolerance. CD103(+) DC could mediate this important function.
研究诱导结肠炎前后小鼠肠道组织中树突状细胞(DC)的可能差异。
通过荧光激活细胞分选(FACS)分析,分析肠道组织、肠系膜淋巴结和脾脏来源的黏膜 DC。分析这些细胞上清液中不同促炎和抗炎细胞因子的分泌情况。对结肠炎动物和健康小鼠的黏膜组织的冷冻切片进行免疫组织化学和免疫荧光染色。
结果表明,来自健康肠固有层(LP)的 DC 表现出不成熟的表型,其特征是共刺激细胞因子表达水平低。与来自脾和肠系膜淋巴结(MLN)的分泌促炎细胞因子的 DC 相反,LP-DC 产生高水平的抗炎细胞因子 IL-10。在 CD4(+)CD62L(+)转移模型或慢性葡聚糖硫酸钠结肠炎中诱导小鼠结肠炎后,可在炎症性结肠组织中观察到激活的 CD80(+) DC 的显著增加。有趣的是,与脾 DC 不同,MLN 和结肠 LP 中的大量 DC 表达黏膜整合素 CD103,而在结肠炎期间该整合素丢失。
肠道 LP 中不成熟 DC 持续分泌抗炎细胞因子可能调节黏膜免疫和耐受之间的稳态平衡。CD103(+) DC 可能介导这一重要功能。