Human CD14+ Macrophages in Intestinal Lamina Propria Exhibit Potent Antigen-Presenting Ability
Human CD14+ Macrophages in Intestinal Lamina Propria Exhibit Potent Antigen-Presenting Ability
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DOI：
10.4049/jimmunol.0804369
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发表时间：
2009-08-01
影响因子：
4.4
通讯作者：
Hibi, Toshifumi
中科院分区：
文献类型：
--
作者：
Kamada, Nobuhiko;Hisamatsu, Tadakazu;Hibi, Toshifumi
肠道APC被认为在维持对有害病原体的应答与诱导对肠道细菌和食物抗原的耐受之间的平衡方面至关重要。最近，一些研究表明存在肠道特异性APC亚群，其具有巨噬细胞和树突状细胞（DC）标志物。这些独特的APC亚群在肠道免疫中发挥着重要作用，特别是对于针对共生细菌的免疫调节。在此，我们研究了一个独特的巨噬细胞亚群，其在人肠固有层（LP）中共表达巨噬细胞（M phi）标志物CD 14和DC标志物CD 209。正常对照组和克罗恩病（CD）患者的LP M phi亚群均诱导幼稚CD 4（+）T细胞和单核细胞来源的DC增殖，并表达视黄酸合成酶视黄醇脱氢酶2和视黄醇脱氢酶10，其以视黄酸依赖性方式诱导T细胞上肠道归巢受体的表达。此外，LP M phi亚群在正常对照组和CD患者中均强烈诱导Th 1细胞分化，轻微诱导Th 17细胞，CD患者的诱导潜力最高。在CD患者中，Th 17，但不是Th 1，诱导LP M phi亚群增强在存在细菌抗原。在正常对照组中未观察到这种增强。通过中和IL-6和IL-1 β抑制LP M phi亚群的Th 17诱导，但通过阻断视黄酸信号传导增强。这些观察结果突出了LP M phi在炎性肠病的炎性部位增强的Th 1和潜在的Th 17分化中的作用。免疫学杂志，2009，183：1724-1731。
Intestinal APCs are considered critical in maintaining the balance between the response against harmful pathogens and the induction of tolerance to commensal bacteria and food Ags. Recently, several studies indicated the presence of gut-specific APC subsets, which possess both macrophage and dendritic cell (DC) markers. These unique APC subsets play important roles in gut immunity, especially for immune regulation against commensal bacteria. Herein, we examined a unique macrophage subset, which coexpressed the macrophage (M phi) marker CD14 and the DC marker CD209 in human intestinal lamina propria (LP). The LP M phi subset in both normal control subjects or Crohn's disease (CD) patients induced proliferation of naive CD4(+) T cells as well as monocyte-derived DCs, and it expressed retinoic acid synthetic enzyme retinaldehyde dehydrogenase 2 and retinol dehydrogenase 10, which induced expression of gut homing receptors on T cells in a retinoic acid-dependent manner. Moreover, the LP M phi subset strongly evoked differentiation of Th1 cells and slightly induced Th17 cells in both normal control subjects and CD patients; the inducing potential was highest in CD patients. In CD patients, Th17, but not Th1, induction by the LP M phi subset was enhanced in the presence of commensal bacteria Ags. This enhancement was not observed in normal control subjects. The Th17 induction by the LP M phi subset was inhibited by neutralization of IL-6 and IL-1 beta, but it was enhanced by blockade of retinoic acid signaling. These observations highlight a role for LP M phi in the enhanced Th1, and potentially in Th17 differentiation, at the inflammatory site of inflammatory bowel diseases. The Journal of Immunology, 2009, 183: 1724-1731.