Authors: Borrelli MA, Warunek JJP, Ann Varghese B, Turner N, Little SR, Turnquist HR
Abstract
Skeletal muscle injuries are a common consequence of physical activity, repetitive movements, and trauma. Regulatory T cells (Treg) act as critical mediators of immune repair response after injury. Thus, 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 an immunomodulatory, 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 injury and enhanced myofiber cross-sectional area in CCL22MP treated limbs. Analysis of the local immune populations revealed augmented Treg concentrations, as well as altered infiltrating myeloid populations towards pro-repair subsets. These findings reveal that amplifying local Treg to damaged areas improves outcomes, thus offering a translationally promising approach after muscle injury.
PMID: 42156970