Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Service d'immunologie biologique (Professeur Batteux), Paris, France.
Nat Commun. 2019 Dec 11;10(1):5670. doi: 10.1038/s41467-019-13636-x.
Chronic inflammation and fibrosis can result from inappropriately activated immune responses that are mediated by macrophages. Macrophages can acquire memory-like characteristics in response to antigen exposure. Here, we show the effect of BCG or low-dose LPS stimulation on macrophage phenotype, cytokine production, chromatin and metabolic modifications. Low-dose LPS training alleviates fibrosis and inflammation in a mouse model of systemic sclerosis (SSc), whereas BCG-training exacerbates disease in this model. Adoptive transfer of low-dose LPS-trained or BCG-trained macrophages also has beneficial or harmful effects, respectively. Furthermore, coculture with low-dose LPS trained macrophages reduces the fibro-inflammatory profile of fibroblasts from mice and patients with SSc, indicating that trained immunity might be a phenomenon that can be targeted to treat SSc and other autoimmune and inflammatory fibrotic disorders.
慢性炎症和纤维化可能是由巨噬细胞介导的异常激活的免疫反应引起的。巨噬细胞可以在抗原暴露时获得类似记忆的特征。在这里，我们展示了 BCG 或低剂量 LPS 刺激对巨噬细胞表型、细胞因子产生、染色质和代谢修饰的影响。低剂量 LPS 训练可减轻系统性硬化症 (SSc) 小鼠模型中的纤维化和炎症，而 BCG 训练则加剧该模型中的疾病。低剂量 LPS 训练或 BCG 训练的巨噬细胞的过继转移也分别具有有益或有害的影响。此外，与低剂量 LPS 训练的巨噬细胞共培养可降低来自 SSc 小鼠和患者的成纤维细胞的纤维炎症特征，表明训练免疫可能是一种可用于治疗 SSc 和其他自身免疫性和炎症性纤维性疾病的现象。
