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Shifts in macrophage cytokine production drive muscle fibrosis

Nature Medicine volume 21, pages 665–666 (2015)Cite this article

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Muscle fibrosis after acute injury can be debilitating, but in chronic muscle disease it can be lethal. A new study reveals that shifts in macrophage phenotype in injured or diseased muscle can influence whether connective tissue production by fibro/adipogenic precursors in muscle is beneficial or pathological.

Skeletal muscles have stressful lives, during which they experience frequent and occasionally severe damage that requires rapid and efficient repair. Typically, the regenerative response to acute muscle injuries is highly effective, drawing on the activation of muscle stem cells (satellite cells) that restore the lost or damaged tissue. Muscle regeneration also requires cells that support myogenesis, including resident mesenchymal cells called fibro/adipogenic precursor cells (FAPs) and macrophages that can regulate satellite cell function1,2,3. However, in chronic muscle diseases such as Duchenne muscular dystrophy (DMD), the regenerative process breaks down and muscle tissue is replaced with fibrotic tissue, with lethal consequences as respiratory and cardiac function become impaired4,5.

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Figure 1: Acute muscle injury leads to FAP proliferation and muscle invasion by myeloid cells.

Marina Corral Spence/Nature Publishing Group

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Authors and Affiliations

  1. and in the Department of Pathology and Laboratory Medicine, James G. Tidball is in the Molecular, Cellular and Integrative Physiology Program, University of California Los Angeles, Los Angeles, California, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California.,

    James G Tidball

  2. Both James G. Tidball and Michelle Wehling-Henricks are in the Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, California.,

    James G Tidball & Michelle Wehling-Henricks

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  1. James G Tidball
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  2. Michelle Wehling-Henricks
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Correspondence to James G Tidball.

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Tidball, J., Wehling-Henricks, M. Shifts in macrophage cytokine production drive muscle fibrosis. Nat Med 21, 665–666 (2015). https://doi.org/10.1038/nm.3896

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