The skin provides a life-sustaining structural and immunological outer barrier of the body and has intrinsic mechanisms that protect the organism from diverse external threats including infections and mechanical injuries. Skin injury induces a complex, dynamic cellular program proceeding in sequential stages of inflammation, tissue growth and differentiation. Cells of the monocyte-macrophage lineage are an integral component of an effective repair response. Blood monocytes that are recruited to the side of tissue damage sense a variety of environmental cues of injured tissue and integrate those into a host protective wound healing response. Given that inappropriate macrophage activation underlies a broad range of pathological processes, from chronic inflammatory skin diseases, type 2 diabetes and cancer, macrophages have emerged as an important target to treat disease. The molecular determinants that precisely control the dynamics of macrophage functional plasticity during healing progression are largely unknown and are just beginning to emerge. Previously we have identified phase-specific functions of wound macrophages, ranging from a pro-inflammatory and angiogenic phenotype in the early healing phase towards a type 2-cytokine-activated pro-fibrotic phenotype in the late phase of healing. We aim to understand the functional relationship between cellular metabolism and the execution of specific repair functions in injury-associated monocytes/macrophages. We will present novel findings showing that different metabolic functions of mitochondria are required to support phase-specific injury-towards-repair programs in wound macrophages. Shaping monocyte/macrophage functions by targeting mitochondria could offer a new approach to pharmaceutically boost regenerative capacity in inflammatory skin diseases.

ESDR241 - Metabolic reprogramming defines myeloid cell function in skin repair

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING