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

Cell. 2013 Apr 11;153(2):376-88. doi: 10.1016/j.cell.2013.02.053.

Abstract

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 in myeloid cells, for rapid clearance of necrotic debris, a process that is necessary for timely and complete regeneration of tissues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cobra Cardiotoxin Proteins
  • Eosinophils / physiology
  • Immunity, Innate*
  • Interleukin-13 / genetics
  • Interleukin-13 / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Mice
  • Muscle Development*
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / injuries*
  • Muscle, Skeletal / physiology
  • Myeloid Cells / metabolism
  • Receptors, Cell Surface / metabolism
  • Regeneration
  • STAT6 Transcription Factor / metabolism
  • Signal Transduction*

Substances

  • Cobra Cardiotoxin Proteins
  • Il4ra protein, mouse
  • Interleukin-13
  • Receptors, Cell Surface
  • STAT6 Transcription Factor
  • Interleukin-4

Associated data

  • GEO/GSE44933