% 0期刊文章% Dharmesh Hirani %克里斯蒂娜·m·Alvira % Soula Danopoulos %一个卡洛斯·米拉% Michele Donato %一个Lu田%茉莉花莫尔%凯瑟琳全垒打%一个错话Selle克里斯蒂娜Vohlen % % Silke诉Koningsbruggen-Rietschel % Verena Barbarino %一个基督教Pallasch % Stefan Rose-John % Margarete Odenthal % Gloria Siavash Mansouri % s Pryhuber %一拉库马岛上%沃纳格% Purvesh Khatri %丹尼斯·阿尔·阿拉姆%一个Jorg Dotsch %米格尔A Alejandre城堡% T Macrophage-derived白介素trans-signaling作为小说在支气管肺的发育不良的发病机制目标2021% % D J R 10.1183/13993003.02248 -2020%欧洲呼吸杂志% P 2002248 % X原理早产儿风险暴露于氧气在支气管肺的发育不良(桶),它的特点是肺增长逮捕。炎症是很重要的,但是机制仍然是难以捉摸的。在这里,我们调查了炎症途径和治疗目标严重临床与实验桶。方法和结果第一,转录组分析in-silico细胞反褶积确定了lung-intrinsic M1-like-driven细胞因子模式在新生鼠氧过多。这些发现证实了基因表达的macrophage-regulating趋化因子(Ccl2, Ccl7, Cxcl5)和标记(白细胞介素6、Il17A Mmp12)。第二,hyperoxia-activated体内il - 6 / STAT3信号测量及相关损失的肺泡上皮II型细胞(ATII)以及增加间充质标记。白细胞介素6空老鼠表现出保存ATII生存,降低myofibroblasts和提高弹性纤维组装,从而使肺生长和保护肺功能。药物抑制全球il - 6信号和il - 6 trans-signaling提升alveolarisation氧过多后和ATII生存。第三,氧过多引发M1-like两极分化,可能通过Klf4;hyperoxia-conditioned巨噬细胞il - 6受损ATII扩散媒介。 Finally, clinical data demonstrate elevated macrophage-related plasma cytokines as potential biomarkers that identify infants receiving oxygen at increased risk of developing BPD. Moreover, macrophage-derived IL6 and active STAT3 were related to loss of epithelial cells in BPD lungs.Conclusion We present a novel IL-6-mediated mechanism by which hyperoxia activates macrophages in immature lungs, impairs ATII homeostasis, and disrupts elastic fiber formation, thereby inhibiting lung growth. The data provide evidence that IL-6 trans-signaling could offer an innovative pharmacological target to enable lung growth in severe neonatal chronic lung disease.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Hirani has nothing to disclose.Conflict of interest: Dr. Alvira has nothing to disclose.Conflict of interest: Dr. Danopoulos has nothing to disclose.Conflict of interest: Dr. Milla reports grants from Proteostasis Inc, grants from Eloxx Pharmaceuticals, grants and personal fees from Vertex Pharmaceuticals, outside the submitted work.Conflict of interest: Dr. Donato has nothing to disclose.Conflict of interest: Dr. Tian has nothing to disclose.Conflict of interest: Dr. Mohr has nothing to disclose.Conflict of interest: Dr. Dinger has nothing to disclose.Conflict of interest: Dr. Vohlen has nothing to disclose.Conflict of interest: Dr. Selle has nothing to disclose.Conflict of interest: Dr. van Koningsbruggen-Rietschel has nothing to disclose.Conflict of interest: Barbarino has nothing to disclose.Conflict of interest: Dr. Pallasch has nothing to disclose.Conflict of interest: Dr. Rose John has nothing to disclose.Conflict of interest: Dr. Odenthal has nothing to disclose.Conflict of interest: Dr. Pryhuber reports grants from NHLBI, during the conduct of the study.Conflict of interest: Siavash Mansouri has nothing to disclose.Conflict of interest: Dr. Savai has nothing to disclose.Conflict of interest: Dr. Seeger reports personal fees from Actelion, personal fees from Abivax, personal fees from Bayer AG, personal fees from Vectura, personal fees from Medspray, personal fees from United Therapeutics, personal fees from Liquidia, personal fees from Pieris, outside the submitted work.Conflict of interest: Dr. Khatri has nothing to disclose.Conflict of interest: Dr. Al Alam has nothing to disclose.Conflict of interest: Dr. Dötsch has nothing to disclose.Conflict of interest: Dr. Alejandre Alcazar has nothing to disclose. %U //www.qdcxjkg.com/content/erj/early/2021/07/01/13993003.02248-2020.full.pdf