Systemic administration of all-trans retinoic acid modulated circulating immune cells but failed to improve healing in a preclinical model of musculoskeletal trauma.

Musculoskeletal trauma is exceedingly common and experiences a high incidence of complications, including bone non-union. Previous studies have implicated a dysregulated systemic immune response after injury as an important factor contributing to complications. We have previously identified a negative correlation between circulating myeloid-derived suppressor cells (MDSCs) and bone regeneration in a rat model of composite bone and muscle trauma. MDSCs are an immature, heterogeneous cell population of myeloid lineage that expands after injury and possesses potent immunosuppressive functions including the inhibition of T cells and expansion of regulatory T cells (Tregs), which could contribute to poor outcomes. As such, they may represent a novel therapeutic target in bone trauma. All-trans retinoic acid (ATRA) is a vitamin A derivative that has previously been shown to reduce MDSCs in cancer models by promoting their differentiation into mature myeloid cell populations. However, ATRA's effects on MDSCs have not been explored in the context of trauma. Here, we investigated the effects of ATRA on peripheral blood immune cells both