Control of innate immune reactions by bronchial epithelial cells

支气管上皮细胞对先天免疫反应的控制

• 批准号: 282130382
• 负责人: Professor Dr. Alexander Dalpke
• 金额: --
• 依托单位: Abteilung Medizinische Mikrobiologie und Hygiene
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/282130382?language=en
• 关键词: Control; innate; immune; reactions; bronchial

Organ specific immunity is controlled by the local microenvironment. Within the airways epithelial cells serve a so far underestimated role in modulating professional immune cells. In previous work we could show that bronchial epithelial cells under homeostatic conditions secrete prostaglandin E2 and reactivate glucocorticoids thereby modulating dendritic cell activity. This resulted in the induction of a phenotype of alternative activation in epithelial cell conditioned dendritic cells that was characterized by inhibition of proinflammatory reactivity. The same phenotype was observed in primary respiratory dendritic cells as examined by gene expression analysis. Moreover, we have analyzed the function of inhibitory Suppressor of Cytokine Signaling-1 (SOCS1) protein. Surprisingly, we observed that SOCS1 translocates to the nucleus where it can be observed at increased expression in epithelial cells from asthma patients. To further study the nuclear function we generated a BAC-transgenic mouse expressing a non-nuclear SOCS1 mutant. In this proposal we want to address the overarching question how those homeostatic regulatory mechanisms change when airway epithelial cells are challenged by infection or antigen encounter. Specifically, want to analyze (i) the importance of PGE2 and glucocorticoid mediated modulatory effects within human airways. (ii) Moreover, we will study how the suppressive interactions between epithelial cells and dendritic cells change upon infection or antigenic challenge in vitro as well as in vivo and in human airway inflammatory diseases. (iii) We intend to analyze the role of endoplasmic reticulum stress for the switch from inhibition to activation within epithelial cells upon stimulation. (iv) Finally, we will examine the function of nuclear SOCS1 for the cell biology of airway epithelial cells using the newly developed mouse model as well as analysis of human airways with inflammatory conditions. The results will improve our understanding of epithelial cell mediated microenvironment regulation within the airways.

器官特异性免疫受局部微环境控制。在气道内，上皮细胞在调节专业免疫细胞中的作用迄今被低估。在以前的工作中，我们可以表明，支气管上皮细胞在稳态条件下分泌前列腺素E2，并重新激活糖皮质激素，从而调节树突状细胞的活性。这导致在上皮细胞条件树突状细胞的替代活化的表型的诱导，其特征在于抑制促炎反应。通过基因表达分析，在原代呼吸道树突状细胞中观察到相同的表型。此外，我们还分析了抑制性细胞因子信号转导抑制因子-1（SOCS 1）蛋白的功能。令人惊讶的是，我们观察到SOCS 1易位到细胞核，在那里可以观察到哮喘患者上皮细胞中的表达增加。为了进一步研究核功能，我们产生了表达非核SOCS 1突变体的BAC转基因小鼠。在这个建议中，我们要解决的首要问题是，当气道上皮细胞受到感染或抗原的挑战时，这些稳态调节机制如何改变。具体来说，想要分析（i）PGE 2和糖皮质激素介导的人体气道调节作用的重要性。(ii)此外，我们将研究上皮细胞和树突状细胞之间的抑制性相互作用如何在体外和体内以及在人类气道炎症性疾病中感染或抗原攻击后发生变化。(iii)我们打算分析的作用，内质网应激的开关从抑制激活上皮细胞内的刺激。(iv)最后，我们将使用新开发的小鼠模型以及对具有炎症条件的人类气道的分析来检查核SOCS 1对于气道上皮细胞的细胞生物学的功能。这一结果将有助于我们更好地理解气道内上皮细胞介导的微环境调节。

项目成果

Crosstalk between glucocorticoids and IL-4 modulates Ym1 expression in alternatively activated myeloid cells.

糖皮质激素和 IL-4 之间的串扰调节替代激活的骨髓细胞中 Ym1 的表达

• DOI: 10.1016/j.imbio.2017.02.003
• 发表时间: 2017
• 期刊: Immunobiology
• 影响因子: 2.8
• 作者: Ng Kuet Leong N;Brombacher F;Dalpke AH;Weitnauer M
• 通讯作者: Weitnauer M

Pseudomonas aeruginosa Modulates the Antiviral Response of Bronchial Epithelial Cells

铜绿假单胞菌调节支气管上皮细胞的抗病毒反应

• DOI: 10.3389/fimmu.2020.00096
• 发表时间: 2020
• 期刊: Frontiers in Immunology
• 影响因子: 7.3
• 作者: Sörensen M;Kantorek J;Byrnes L;Boutin S;Mall MA;Lasitschka F;Zabeck H;Nguyen D;Dalpke AH
• 通讯作者: Dalpke AH