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Trained immunity modulates inflammation-induced fibrosis

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  • Mohamed Jeljeli

    (Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité
    Assistance Publique–Hôpitaux de Paris (AP–HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Service d’immunologie biologique (Professeur Batteux))

  • Luiza Gama Coelho Riccio

    (Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité
    Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina FMUSP, Universidade de São Paulo)

  • 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
    Assistance Publique–Hôpitaux de Paris (AP–HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Service de rhumatologie)

  • Niloufar Kavian

    (Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité
    Assistance Publique–Hôpitaux de Paris (AP–HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Service d’immunologie biologique (Professeur Batteux)
    Hong Kong University-Pasteur Research Pole, School of Public Health, The University of Hong Kong)

  • Frédéric Batteux

    (Institut Cochin, INSERM U1016, Université Paris Descartes, Sorbonne Paris Cité
    Assistance Publique–Hôpitaux de Paris (AP–HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, Service d’immunologie biologique (Professeur Batteux))

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.

Suggested Citation

  • Mohamed Jeljeli & Luiza Gama Coelho Riccio & Ludivine Doridot & Charlotte Chêne & Carole Nicco & Sandrine Chouzenoux & Quentin Deletang & Yannick Allanore & Niloufar Kavian & Frédéric Batteux, 2019. "Trained immunity modulates inflammation-induced fibrosis," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13636-x
    DOI: 10.1038/s41467-019-13636-x
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