IL-10-dependent partial refractoriness to Toll-like receptor stimulation modulates gut mucosal dendritic cell function
IL-10-dependent partial refractoriness to Toll-like receptor stimulation modulates gut mucosal dendritic cell function
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DOI：
10.1002/eji.200737909
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发表时间：
2008-06-01
影响因子：
5.4
通讯作者：
Mowat, Allan McI.
中科院分区：
文献类型：
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作者：
Monteleone, Ivan;Platt, Andrew M.;Mowat, Allan McI.
肠道免疫系统对大多数抗原的默认反应是诱导免疫耐受，这与持续接触TLR和其他模式识别受体的配体很难调和。我们以前发现，正常小鼠肠道固有层的树突状细胞(DC)可能具有固有的耐受性，在这里，我们探索了这可能与Toll样受体(TLR)的表达和功能的关系。固有层DC的TLR2、TLR3、TLR4和TLR9蛋白表达水平高于脾和MLN DC，肠道表达TLR2、3、4和9的DC主要为CD11c(Lo)、II类MHClo、CD103(-)、CD11b(-)和F4/80(-)。TLR固有层DC在小肠上部表达较低，远端小肠和结肠表达较高。新鲜分离的固有层DC表达部分CD40、CD80、CD86和功能性CCR7。经TLR刺激后，CD11c(Lo)上调，而CD1lc(Hi)Lp DC不上调。然而，在TLR结扎的反应中，这两个亚群几乎都没有诱导IL-12的产生。这与固有的IL-10产生有关，并可通过阻断IL-10的功能而逆转。因此，IL-10可以维持LP DC对TLR结扎的部分无反应状态，使其在肠道免疫内稳态中发挥关键作用。
The default response of the intestinal immune system to most antigens is the induction of immunological tolerance, which is difficult to reconcile with the constant exposure to ligands for TLR and other pattern recognition receptors. We showed previously that dendritic cells (DC) from the lamina propria of normal mouse intestine may be inherently tolerogenic and here we have explored how this might relate to the expression and function of Toll-like receptors (TLR). Lamina propria (LP) DC showed higher levels of TLR 2, 3, 4 and 9 protein expression than spleen and MLN DC, with most TLR-expressing DC in the gut being CD11c(lo), class II MHClo, CD103(-), CD11b(-) and F4/80(-). TLR expression by lamina propria DC was low in the upper small intestine and higher in distal small intestine and colon. Freshly isolated lamina propria DC expressed some CD40, CD80, CD86 and functional CCR7. These were up-regulated on CD11c(lo), but not on CD1lc(hi) LP DC by stimulation via TLR. However, there was little induction of IL-12 by either subset in response to TLR ligation. This was associated with constitutive IL-10 production and was reversed by blocking IL-10 function. Thus, IL-10 may maintain LP DC in a partially unresponsive state to TLR ligation, allowing them to have a critical role in immune homeostasis in the gut.