Regulatory T Cell Attracting Therapy Accelerates Skeletal Muscle Functional Recovery Following Injury

Skeletal muscle injuries are a common consequence of physical activity, repetitive movements, and trauma. Regulatory T cells (Treg) have recently been identified as critical mediators of immune repair response after injury, and treatments effectively targeting Treg may accelerate injury resolution. CCL22 is a chemokine that recruits CCR4-expressing cells, particularly Treg, to sites of inflammation or immune regulation, such as tumor microenvironments. When a sustained release formulation of polymeric microparticles (MP) delivering CCL22 (CCL22MP), was administered after cardiotoxin (CTx)-mediated muscle injury, significantly improved limb function was observed on days 3 and 5 post injury. Histologic evaluation of the injured limbs showed reduced area of injury in CCL22MP treated limbs. Analysis of the local immune populations revealed augmented Treg concentrations, as well as increased myeloid derived suppressor cell and neutrophil frequency. These findings reveal that amplifying local Treg to damaged areas improves outcomes, thus offering a translationally promising approach after muscle injury.