title: Type 2 innate signals stimulate fibro/adipogenic progenitors to facilitate muscle regeneration.
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.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158-9001, USA.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Heredia
authors.forename: Lata
authors.initials: L
authors.lastname: Mukundan
authors.forename: Francis M
authors.initials: FM
authors.lastname: Chen
authors.forename: Alisa A
authors.initials: AA
authors.lastname: Mueller
authors.forename: Rahul C
authors.initials: RC
authors.lastname: Deo
authors.forename: Richard M
authors.initials: RM
authors.lastname: Locksley
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Rando
authors.forename: Ajay
authors.initials: A
authors.lastname: Chawla
mesh_terms: D000818:Animals; D004179:Cobra Cardiotoxin Proteins; D004804:Eosinophils / Q000502:physiology; D007113:Immunity, Innate; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology* / Q000293:injuries* / Q000502:physiology; D022423:Myeloid Cells / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D012038:Regeneration; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D004179:Cobra Cardiotoxin Proteins; D018793:Interleukin-13; D015847:Interleukin-4; D011956:Receptors, Cell Surface; D050800:STAT6 Transcription Factor; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit