Ferris Stephen T, Zakharov Pavel N, Wan Xiaoxiao, Calderon Boris, Artyomov Maxim N, Unanue Emil R, Carrero Javier A
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
J Exp Med. 2017 Aug 7;214(8):2369-2385. doi: 10.1084/jem.20170074. Epub 2017 Jun 19.
We examined the transcriptional profiles of macrophages that reside in the islets of Langerhans of 3-wk-old non-obese diabetic (NOD), NOD., and B6.g7 mice. Islet macrophages expressed an activation signature with high expression of , , and MHC-II at both the transcript and protein levels. These features are common with barrier macrophages of the lung and gastrointestinal tract. Moreover, injection of lipopolysaccharide induced rapid inflammatory gene expression, indicating that blood stimulants are accessible to the macrophages and that these macrophages can sense them. In NOD mice, the autoimmune process imparted an increased inflammatory signature, including elevated expression of chemokines and chemokine receptors and an oxidative response. The elevated inflammatory signature indicates that the autoimmune program was active at the time of weaning. Thus, the macrophages of the islets of Langerhans are poised to mount an immune response even at steady state, while the presence of the adaptive immune system elevates their activation state.
我们研究了3周龄非肥胖糖尿病（NOD）小鼠、NOD.小鼠和B6.g7小鼠胰岛中巨噬细胞的转录谱。胰岛巨噬细胞在转录水平和蛋白质水平均表现出激活特征，即 、 和MHC-II的高表达。这些特征与肺和胃肠道的屏障巨噬细胞相同。此外，注射脂多糖可诱导炎症基因快速表达，这表明巨噬细胞可接触到血液中的刺激物，并且这些巨噬细胞能够感知它们。在NOD小鼠中，自身免疫过程导致炎症特征增强，包括趋化因子和趋化因子受体表达升高以及氧化反应。炎症特征增强表明自身免疫程序在断奶时就已活跃。因此，即使在稳态下，胰岛巨噬细胞也准备好启动免疫反应，而适应性免疫系统的存在则会提高它们的激活状态。
