Local IL-10 delivery modulates the immune response and enhances repair of volumetric muscle loss muscle injury
Tai Huynh, Cassandra Reed, Zain Blackwell, Payton Phelps, Luis Carlos Pinzon Herrera, Jorge Almodóvar, David A. Zaharoff, Jeffrey C. Wolchok
Abstract
Abstract This study was designed to test the hypothesis that in addition to repairing the architectural and cellular cues via regenerative medicine, the delivery of immune cues (immunotherapy) may be needed to enhance regeneration following volumetric muscle loss (VML) injury. We identified IL-10 signaling as a promising immunotherapeutic target. To explore the impact of targeting IL-10 signaling, tibialis anterior (TA) VML injuries were created and then treated in rats using autologous minced muscle (MM). Animals received either recombinant rat IL-10 or phosphate buffered saline (PBS) controls injections at the site of VML repair beginning 7 days post injury (DPI) and continuing every other day (4 injections total) until 14 DPI. At 56 DPI (study endpoint), significant improvements to TA contractile torque (82% of uninjured values & 170% of PBS values), TA mass, and myofiber size in response to IL-10 treatment were detected. Whole transcriptome analysis at 14 DPI revealed activation of IL-10 signaling, muscle hypertrophy, and lymphocytes signaling pathways. Expression of ST2, a regulatory T (T reg ) cell receptor, was dramatically increased at the VML repair site in response to IL-10 treatment when compared to PBS controls. The findings suggest that the positive effect of delayed IL-10 delivery might be due to immuno-suppressive T reg cell recruitment.