Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes.
Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes.
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DOI：
10.1038/ncomms8802
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发表时间：
2015-07-21
影响因子：
16.6
通讯作者：
Tanaka M
中科院分区：
文献类型：
--
作者：
Asano K;Takahashi N;Ushiki M;Monya M;Aihara F;Kuboki E;Moriyama S;Iida M;Kitamura H;Qiu CH;Watanabe T;Tanaka M
固有层（LP）巨噬细胞不断暴露于共生细菌中，并以白细胞介素(IL)-10依赖的方式对这些抗原产生抗性。然而，区分有害细菌入侵与与细菌和平共处的机制仍然难以捉摸。在这里，我们发现CD169+巨噬细胞不存在于绒毛尖端，而是存在于LP微环境的底端。粘膜损伤后，CD169+巨噬细胞通过分泌CCL8募集炎性单核细胞。选择性消耗CD169+巨噬细胞或给予中和性抗ccl8抗体可改善实验性结肠炎小鼠的症状。总的来说，我们确定了一个lp巨噬细胞亚群，它与粘膜损伤和炎症单核细胞募集有关。我们的研究结果表明，CD169+巨噬细胞来源的CCL8可作为屏障防御崩溃的紧急警报，并且是抑制粘膜损伤的有希望的靶点。巨噬细胞和树突状细胞驻留在固有层参与控制粘膜免疫平衡。在这里，作者发现CD169+巨噬细胞通过分泌细胞因子CCL8介导单核细胞的募集，从而促进了DSS结肠炎的炎症。
Lamina propria (LP) macrophages are constantly exposed to commensal bacteria, and are refractory to those antigens in an interleukin (IL)-10-dependent fashion. However, the mechanisms that discriminate hazardous invasion by bacteria from peaceful co-existence with them remain elusive. Here we show that CD169+ macrophages reside not at the villus tip, but at the bottom-end of the LP microenvironment. Following mucosal injury, the CD169+ macrophages recruit inflammatory monocytes by secreting CCL8. Selective depletion of CD169+ macrophages or administration of neutralizing anti-CCL8 antibody ameliorates the symptoms of experimentally induced colitis in mice. Collectively, we identify an LP-resident macrophage subset that links mucosal damage and inflammatory monocyte recruitment. Our results suggest that CD169+ macrophage-derived CCL8 serves as an emergency alert for the collapse of barrier defence, and is a promising target for the suppression of mucosal injury. Macrophages and dendritic cells residing in the lamina propria are involved in controlling mucosal immune balance. Here, the authors identify CD169+ macrophages as contributors to the inflammation of DSS colitis through their role in mediating the recruitment of monocytes by secreting the cytokine CCL8.