Type 2 innate signals stimulate fibro/adipogenic progenitors to facilitate muscle regeneration

By J. Heredia, Lata Mukundan, Francis M. Chen, Alisa A. Mueller, Rahul C. Deo, R. Locksley, T. Rando, A. Chawla. Cell, 2013

774 citations recorded by the source corpus.

SUMMARY In vertebrates, activation of innate immunity is an early response to injury, implicating it in the regenerative process. However, the mechanisms by which innate signals might regulate stem cell functionality are unknown. Here we demonstrate that type 2 innate immunity is required for regeneration of skeletal muscle after injury. Muscle damage results in rapid recruitment of eosinophils, which secrete IL-4 to activate the regenerative actions of muscle resident fibro/adipocyte progenitors (FAPs). In FAPs, IL-4/IL-13 signaling serves as a key switch to control their fate and functions. Activation of IL-4/IL-13 signaling promotes proliferation of FAPs to support myogenesis, while inhibiting their differentiation into adipocytes. Surprisingly, type 2 cytokine signaling is also required in FAPs, but not myeloid cells, for rapid clearance of necrotic debris, a process that is necessary for timely and complete regeneration of tissues.

Subfields: Genetics, Molecular Biology, Rheumatology

View Paper: https://www.semanticscholar.org/paper/860d5a9ff7cbf30d2f94137e1723d4f1da8bebce

How researchers see this paper

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In Genetics

1. J. Hawley
2. F. Powrie
3. D. Artis
4. B. Spiegelman

In Molecular Biology

1. B. Spiegelman
2. E. Rosen
3. Mark P. Jedrychowski
4. F. Powrie
5. Steven P. Gygi
6. J. Hawley
7. M. Colonna
8. D. Artis

Citations in the corpus

• Innate Lymphoid Cells: 10 Years On. (2018, positive): “In this way, FAPs supported myogenesis and the regeneration of skeletal muscle after injury driven by a type 2 immune program (Heredia et al., 2013).”
• Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis (2014, background): “The important role of eosinophils and M2 macrophages in other repair processes, including those in damaged muscle (Arnold et al., 2007; Heredia et al., 2013) and liver (Goh et al., 2013), suggests additional interesting therapeutic applications.”
• What We Talk About When We Talk About Fat (2014, positive): “clearing necrotic debris, and supporting myogenesis (Heredia et al., 2013; Joe et al., 2010).”