Table_7_Differential regulation of Type 1 and Type 2 mouse eosinophil activation by apoptotic cells.xlsx

Eosinophils are multifunctional, evolutionary conserved leukocytes that are involved in a plethora of responses ranging from regulation of tissue homeostasis, host defense and cancer. Although eosinophils have been studied mostly in the context of Type 2 inflammatory responses, it is now evident that they participate in Type 1 inflammatory responses and can respond to Type 1 cytokines such as IFN-γ. Notably, both Type 1- and Type 2 inflammatory environments are characterized by tissue damage and cell death. Collectively, this raises the possibility that eosinophils can interact with apoptotic cells, which can alter eosinophil activation in the inflammatory milieu. Herein, we demonstrate that eosinophils can bind and engulf apoptotic cells. We further show that exposure of eosinophils to apoptotic cells induces marked transcriptional changes in eosinophils, which polarize eosinophils towards an anti-inflammatory phenotype that is associated with wound healing and cell migration. Using an unbiased RNA sequencing approach, we demonstrate that apoptotic cells suppress the inflammatory responses of eosinophils that were activated with IFN-γ + E. coli (e.g., Type 1 eosinophils) and augment IL-4-induced eosinophil activation (e.g., Type 2 eosinophils). These data contribute to the growing understanding regarding the heterogeneity of eosinophil activation patterns and highlight apoptotic cells as potential regulators of eosinophil polarization.

嗜酸性粒细胞（Eosinophils）是一类多功能且进化保守的白细胞，参与涵盖组织稳态调控、宿主防御及肿瘤发生在内的多种生理病理反应。尽管此前对嗜酸性粒细胞的研究多围绕2型炎症反应（Type 2 inflammatory responses）展开，但现有研究已证实，其可参与1型炎症反应（Type 1 inflammatory responses），并能对IFN-γ等1型细胞因子产生应答。值得注意的是，1型与2型炎症环境均以组织损伤和细胞死亡为典型特征。综上，这提示嗜酸性粒细胞可能与凋亡细胞发生相互作用，而该相互作用可在炎症微环境中改变嗜酸性粒细胞的活化状态。
本研究证实，嗜酸性粒细胞能够结合并吞噬凋亡细胞。进一步研究表明，嗜酸性粒细胞接触凋亡细胞后会发生显著的转录组变化，使其极化为与伤口愈合及细胞迁移相关的抗炎表型。通过无偏倚RNA测序（unbiased RNA sequencing）技术，我们证实凋亡细胞可抑制经IFN-γ + 大肠杆菌（E. coli）活化的嗜酸性粒细胞（即1型嗜酸性粒细胞）的炎症应答，并增强IL-4诱导的嗜酸性粒细胞活化（即2型嗜酸性粒细胞）。本研究数据进一步深化了我们对嗜酸性粒细胞活化模式异质性的认知，并凸显凋亡细胞作为嗜酸性粒细胞极化潜在调控因子的潜力。