IRF4-driven monocyte-derived APC-Treg axis promotes wound healing, impaired in diabetes

Despite extensive research on macrophage roles in wound healing, the specific contribution of dermal monocyte (Mo)-derived antigen presenting cells (APC) remains poorly understood, particularly in the context of diabetic wound healing. Chronic diabetes significantly impairs wound repair, leading to severe complications. Current treatments often fall short in addressing the complex cellular and molecular dysregulation underlying this impairment. This study investigates the overlooked role of Mo-derived APCs and their interaction with T regulatory cells (Treg) as a potential therapeutic target.

Researchers utilized non-diabetic, diabetic, Ccr2 knockout, and Mo-specific Irf4 knockout mice models. They employed scRNAseq and flow cytometry to identify and characterize wound APC populations. Adoptive transfer experiments with bone marrow Mo were performed to confirm Mo origin and the role of Irf4. To assess therapeutic potential, recombinant IL-27 was locally administered into wounds of Irf4 knockout mice. Primary endpoints included quantification of wound APCs, activated Treg cells, and overall wound healing progression.