ILC2s Promote Fibrosis-Associated Gene Expression

A new study, led by scientists at the University of California, reveals how chronic inflammation promotes muscle fibrosis, which could inform the development of new therapies for patients suffering from Duchenne muscular dystrophy (DMD). 

"In our study we found the interaction between two types of cells—a novel stromal progenitor, which is similar to a stem cell, and group 2 innate lymphoid cells (ILC2), which are a type of immune cell that reside in skeletal muscle—promotes the invasion of white blood cells in muscle. This condition is associated with the elevation of genes that promote muscle tissue scarring found in DMD," said lead author Jenna Kastenschmidt, of the paper published in Cell Reports. 

The new study not only reveals the interaction of cells contributing to DMD, but it illuminates how muscle eosinophilia is regulated. In this study, researchers found that eosinophils were elevated in DMD muscle compared to control patients. In addition, researchers found the deletion of ILC2s in dystrophic mice mitigated muscle eosinophilia, reducing the expression of genes associated with muscle fibrosis. These findings contribute to the understanding of the complex regulation of muscle inflammation and fibrosis during muscular dystrophy.

"By further defining the interaction between skeletal muscle-resident immune and stromal cells, we can better understand how chronic inflammation promotes muscle fibrosis and, more importantly, we can facilitate development of novel therapies for DMD," said senior author Armando Villalta. Ongoing work from Villalta's lab continues to focus on how distinct facets of the immune system regulate DMD pathogenesis and how these processes influence the efficacy and long-term stability of gene replacement therapy.