Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, Scotland.
School of Medical Sciences, Örebro University, Örebro, Sweden.
Eur J Immunol. 2018 Jul;48(7):1181-1187. doi: 10.1002/eji.201747318. Epub 2018 May 8.
Macrophages play a crucial role in maintaining homeostasis in the intestine, but the underlying mechanisms have not yet been elucidated fully. Here, we show for the first time that mature intestinal macrophages in mouse intestine express high levels of αvβ5 integrin, which acts as a receptor for the uptake of apoptotic cells and can activate molecules involved in several aspects of tissue homeostasis such as angiogenesis and remodeling of the ECM. αvβ5 is not expressed by other immune cells in the intestine, is already present on intestinal macrophages soon after birth, and its expression is not dependent on the microbiota. In adults, αvβ5 is induced during the differentiation of monocytes in response to the local environment and it confers intestinal macrophages with the ability to promote engulfment of apoptotic cells via engagement of the bridging molecule milk fat globule EGF-like molecule 8. In the absence of αvβ5, there are fewer monocytes in the mucosa and mature intestinal macrophages have decreased expression of metalloproteases and IL 10. Mice lacking αvβ5 on haematopoietic cells show increased susceptibility to chemical colitis and we conclude that αvβ5 contributes to the tissue repair by regulating the homeostatic properties of intestinal macrophages.
巨噬细胞在维持肠道内稳态方面发挥着至关重要的作用,但其中的潜在机制尚未完全阐明。在这里,我们首次表明,成熟的肠道巨噬细胞在小鼠肠道中表达高水平的αvβ5 整合素,该整合素作为摄取凋亡细胞的受体,并能激活参与组织稳态多个方面的分子,如血管生成和 ECM 的重塑。αvβ5 不在肠道中的其他免疫细胞中表达,在出生后不久就存在于肠道巨噬细胞中,其表达不依赖于微生物群。在成年期,αvβ5 在单核细胞分化过程中被诱导,以响应局部环境,使其具有通过桥接分子乳脂肪球 EGF 样分子 8 的结合来促进凋亡细胞吞噬的能力。在缺乏 αvβ5 的情况下,黏膜中的单核细胞较少,成熟的肠道巨噬细胞表达的金属蛋白酶和 IL 10 减少。造血细胞缺乏 αvβ5 的小鼠对化学性结肠炎的易感性增加,我们得出结论,αvβ5 通过调节肠道巨噬细胞的稳态特性来促进组织修复。