Modulation of dendritic cell phenotype and function in an in vitro model of the intestinal epithelium
Modulation of dendritic cell phenotype and function in an in vitro model of the intestinal epithelium
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DOI：
10.1002/eji.200535497
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发表时间：
2006-04-01
影响因子：
5.4
通讯作者：
Ghosh, S
中科院分区：
文献类型：
--
作者：
Butler, M;Ng, CY;Ghosh, S
树突状细胞网络（DC）可以在靠近肠道Peyer's斑块上的上皮细胞附近检测到。与来自全身淋巴结的DC相比，肠道DC表现出不同的表型（MHC和共刺激分子相对较低，IL-10和TGF β较高），并可能在维持对肠道抗原的耐受性中发挥作用。我们表明，在体外极化上皮细胞单层的存在下，诱导了类似的表型。单核细胞来源的DC与Caco-2肠上皮单层共培养24小时。共培养导致DC的MHCⅱ类、CD86和CD80的表达降低，T细胞刺激能力差。细胞因子谱显示炎症细胞因子产生水平降低，由于自分泌TGF β产生水平增加，共培养DC对toll样受体（TLR2, 4和6）刺激的敏感性降低。然而，共培养DC的表型变化不能通过去除凋亡细胞或添加抗tgf β抗体来阻断，这表明其他可溶性因子参与了DC的调节。因此，极化上皮细胞单层创造了一个“耐受性”环境，调节DC的活性。这些结果强调了粘膜表面上皮微环境的调节重要性。
A network of dendritic cells (DC) can be detected in close proximity to the epithelial cells overlying Peyer's patches in the gut. Intestinal DC show distinct phenotypes as compared to DC from the systemic lymph nodes (relatively low MHC and costimulatory molecules and high IL-10 and TGF beta) and may play a role in maintaining tolerance to enteric antigens. We show that a similar phenotype is induced in the presence of a polarised epithelial cell monolayer in vitro. Monocyte-derived DC were co-cultured with Caco-2 intestinal epithelial monolayers for 24 h. Co-culture resulted in DC with reduced expression of MHC class II, CD86, and CD80, and poor T cell stimulatory capacity. Cytokine profiles showed reduced levels of inflammatory cytokine production, and co-cultured DC were less sensitive to stimulation via Toll-like receptors (TLR2, 4, and 6) as a result of increased levels of autocrine TGF beta production. However, phenotypic changes in co-cultured DC could not be blocked by removal of apoptotic cells or addition of anti-TGF beta antibodies, suggesting that other soluble factors are involved in DC modulation. Thus, polarised epithelial cell monolayers create a 'tolerogenic, environment which modulates the activity of DC. These results highlight the regulatory importance of the epithelial microenvironment at mucosal surfaces.