英国牛津大学Irina A. Udalova研究团队发现，不同的转录因子网络控制中性粒细胞驱动的炎症。相关论文于2021年7月19日在线发表于国际学术期刊《自然—免疫学》。

为了确定在小鼠模型中形成这些反应的转录因子网络，研究人员整合了急性炎症期间中性粒细胞的转录和染色质分析。结果显示，在两个过渡阶段有活跃的染色质重塑：骨髓到血液和血液到组织。对不同可及区域的分析显示了与控制中性粒细胞炎症反应有关的不同的推定转录因子组。利用体内外方法，研究人员证实RUNX1和KLF6调节中性粒细胞的成熟，而RELB、IRF5和JUNB驱动中性粒细胞效应器反应，RFX2和RELB促进生存。

通过靶向这些因素之一JUNB来干扰中性粒细胞的激活，可以减少心肌梗死小鼠模型中的病理性炎症。因此，这项研究描绘出了急性炎症中中性粒细胞反应的转录控制的蓝图，并为疾病中中性粒细胞功能的阶段性治疗调控提供了可能性。

据介绍，中性粒细胞根据其发育阶段、激活状态和组织微环境显示出不同的基因表达模式。

附：英文原文

Title: Distinct transcription factor networks control neutrophil-driven inflammation

Author: Tariq E. Khoyratty, Zhichao Ai, Ivan Ballesteros, Hayley L. Eames, Sara Mathie, Sandra Martn-Salamanca, Lihui Wang, Ashleigh Hemmings, Nicola Willemsen, Valentin von Werz, Annette Zehrer, Barbara Walzog, Erinke van Grinsven, Andres Hidalgo, Irina A. Udalova

Issue&Volume: 2021-07-19

Abstract: Neutrophils display distinct gene expression patters depending on their developmental stage, activation state and tissue microenvironment. To determine the transcription factor networks that shape these responses in a mouse model, we integrated transcriptional and chromatin analyses of neutrophils during acute inflammation. We showed active chromatin remodeling at two transition stages: bone marrow–to-blood and blood-to-tissue. Analysis of differentially accessible regions revealed distinct sets of putative transcription factors associated with control of neutrophil inflammatory responses. Using ex vivo and in vivo approaches, we confirmed that RUNX1 and KLF6 modulate neutrophil maturation, whereas RELB, IRF5 and JUNB drive neutrophil effector responses and RFX2 and RELB promote survival. Interfering with neutrophil activation by targeting one of these factors, JUNB, reduced pathological inflammation in a mouse model of myocardial infarction. Therefore, our study represents a blueprint for transcriptional control of neutrophil responses in acute inflammation and opens possibilities for stage-specific therapeutic modulation of neutrophil function in disease.

DOI: 10.1038/s41590-021-00968-4

Source: https://www.nature.com/articles/s41590-021-00968-4