No longer regarded simply as end-stage cytotoxic effectors, eosinophils are now recognized as complex cells with unique phenotypes that develop in response stimuli in the local microenvironment. In our previous study, we documented eosinophil infiltration in damaged muscle characteristic of dystrophin-deficient (mdx) mice that model Duchenne muscular dystrophy. Specifically, we found that eosinophils did not promote the generation of muscle lesions, as these persisted in eosinophil-deficient mdx.PHIL mice. To obtain additional insight into these findings, we performed RNA sequencing of eosinophils isolated from muscle tissue of mdx, IL5tg, and mdx.IL5tg mice. We observed profound up-regulation of classical effector proteins (major basic protein-1, eosinophil peroxidase, and eosinophil-associated ribonucleases) in eosinophils isolated from lesion-free muscle from IL5tg mice. By contrast, we observed significant up-regulation of tissue remodeling genes, including proteases, extracellular matrix components, collagen, and skeletal muscle precursors, as well as the immunomodulatory receptor, Trem2, in eosinophils isolated from skeletal muscle tissue from the dystrophin-deficient mdx mice. Although the anti-inflammatory properties of Trem2 have been described in the monocyte/macrophage lineage, no previous studies have documented its expression in eosinophils. We found that Trem2 was critical for full growth and differentiation of bone marrow-derived eosinophil cultures and full expression of TLR4. Immunoreactive Trem2 was also detected on human peripheral blood eosinophils at levels that correlated with donor body mass index and total leukocyte count. Taken together, our findings provide important insight into the immunomodulatory and remodeling capacity of mouse eosinophils and the flexibility of their gene expression profiles in vivo.

中文翻译：

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组织嗜酸性粒细胞中髓样细胞 2 (Trem2) 上表达的触发受体的差异表达

嗜酸性粒细胞不再被简单地视为末期细胞毒性效应物，现在被认为是具有独特表型的复杂细胞，这些细胞在局部微环境中的响应刺激中产生。在我们之前的研究中，我们记录了以杜氏肌营养不良症为模型的肌营养不良蛋白缺陷 (mdx) 小鼠的受损肌肉中的嗜酸性粒细胞浸润。具体来说，我们发现嗜酸性粒细胞不会促进肌肉损伤的产生，因为这些在嗜酸性粒细胞缺乏的 mdx.PHIL 小鼠中持续存在。为了进一步了解这些发现，我们对从 mdx、IL5tg和 mdx 的肌肉组织中分离的嗜酸性粒细胞进行了 RNA 测序。IL5tg老鼠。我们观察到从IL5tg小鼠的无损伤肌肉中分离的嗜酸性粒细胞中经典效应蛋白（主要碱性蛋白-1、嗜酸性粒细胞过氧化物酶和嗜酸性粒细胞相关核糖核酸酶）的显着上调。相比之下，我们观察到组织重塑基因的显着上调，包括蛋白酶、细胞外基质成分、胶原蛋白和骨骼肌前体，以及免疫调节受体Trem2，在从肌营养不良蛋白缺陷 mdx 的骨骼肌组织中分离的嗜酸性粒细胞中。老鼠。尽管已在单核细胞/巨噬细胞谱系中描述了 Trem2 的抗炎特性，但之前的研究没有记录其在嗜酸性粒细胞中的表达。我们发现Trem2对骨髓来源的嗜酸性粒细胞培养物的完全生长和分化以及 TLR4 的完全表达至关重要。还在人外周血嗜酸性粒细胞上检测到免疫反应性 Trem2，其水平与供体体重指数和总白细胞计数相关。总之，我们的研究结果提供了对小鼠嗜酸性粒细胞的免疫调节和重塑能力及其体内基因表达谱的灵活性的重要见解。