Neutrophil and natural killer cell imbalances prevent muscle stem cell–mediated regeneration following murine volumetric muscle loss

• DOI: 10.1073/pnas.2111445119
• Publication Date: 2022-04-04T15:27:16Z
• Authors: Jacqueline A. Lar...; Paula M. Fraczek; Sarah J. Kurpiers; Benjamin A. Yang; Carol Davis; Jesus A. Castor-M...; Kaitlyn Sabin; Shannon Anderson; Julia Harrer; Matthew Hall; Susan V. Brooks; Young C. Jang; Nick Willett; Lonnie D. Shea; Carlos A. Aguilar
• Keywords: 0301 basic medicine; Satellite Cells, Skeletal Muscle; Neutrophils; Biological Sciences; Fibrosis; 3. Good health; Killer Cells, Natural; Mice; 03 medical and health sciences; Muscular Diseases; Neutrophil Infiltration; Transforming Growth Factor beta; Animals; Regeneration; Muscle, Skeletal

SignificanceSkeletal muscle is one of the largest tissues in the body and can regenerate when damaged through a population of resident muscle stem cells. A type of muscle trauma called volumetric muscle loss overwhelms the regenerative capacity of muscle stem cells and engenders fibrotic supplantation. A comparison of muscle injuries resulting in regeneration or fibrosis revealed that intercellular communication between neutrophils and natural killer cells impacts muscle stem cell-mediated repair. Perturbation of neutrophil–natural killer cell interactions resulted in a variation of healing outcomes and suggested that immunomodulatory interventions can be effective to prevent aberrant healing outcomes.