Trained immunity modulates inflammation-induced fibrosis

Nature Communications - Tập 10 Số 1
Mohamed Jeljeli1, Luiza Gama Coelho Riccio1, Ludivine Doridot1, Charlotte Chêne1, Carole Nicco1, Sandrine Chouzenoux1, Quentin Deletang1, Yannick Allanore1, Niloufar Kavian2, Frédéric Batteux1
1Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
2Assistance Publique–Hôpitaux de Paris (AP–HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Service d’immunologie Biologique (Professeur Batteux), Paris, France

Tóm tắt

AbstractChronic 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.

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