Trained immunity modulates inflammation-induced fibrosis

Mohamed Jeljeli, Luiza Gama Coelho Riccio, Ludivine Doridot, Charlotte Chêne, Carole Nicco, Sandrine Chouzenoux, Quentin Deletang, Yannick Allanore, Niloufar Kavian and Frédéric Batteux ()
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Mohamed Jeljeli: Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité
Luiza Gama Coelho Riccio: Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité
Ludivine Doridot: Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité
Charlotte Chêne: Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité
Carole Nicco: Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité
Sandrine Chouzenoux: Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité
Quentin Deletang: Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité
Yannick Allanore: Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité
Niloufar Kavian: Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité
Frédéric Batteux: Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-13636-x

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