A prenatal immune programme that helps build skin tissue in the womb appears to be reactivated in adults with eczema and psoriasis, potentially driving inflammation. The researcher has found that certain macrophages and blood vessel cells in developing skin switch on a shared set of genes that guide immune cells into the tissue. In adults with inflammatory skin disease, the same cells and gene signature reappear, suggesting the body is reusing an embryonic recruitment system to fuel chronic inflammation. This matters because current treatments for eczema and psoriasis often suppress the immune system broadly, rather than targeting the specific molecular pathways that sustain inflammation. If the researcher can map exactly where and how these prenatal programmes are reactivated, it could reveal new drug targets that block inflammatory cell entry without disabling the entire immune response. The project is fundamental science—it asks how developmental gene programmes are repurposed in disease. A detailed understanding of these macrophage-endothelial interactions could eventually inform tissue engineering for skin repair and lead to more precise therapies for common inflammatory skin conditions.
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Our immune system develops early in prenatal life in a relatively pathogen-free environment. We recently identified gene expression programmes involving macrophage-vascular endothelial cell interactions that are functionally predicted to seed leukocytes into tissue during development. Intriguingly, we found that these cells are expanded in adult patients with inflammatory skin disease, have the same gene expression signature as their embryonic counterparts and therefore likely support leukocyte recruitment into tissue during inflammation. I aim to unravel the role of the prenatal macrophage-endothelial gene programmes during tissue morphogenesis and in inflammatory disease. I will dissect the locations of these macrophages and vascular endothelial cells and their gene expression programmes in situ using spatially-resolved transcriptomics analyses. I will compare skin from prenatal samples and patients with two common inflammatory skin diseases, atopic dermatitis and psoriasis, to define the spatial and molecular regulation of these programmes during skin morphogenesis and in disease. I will use skin organoids for mechanistic validation studies on the regulation of the macrophage-endothelial gene programmes following disease-simulating conditions and how macrophages support organoid differentiation and leukocyte recruitment. A detailed understanding of developmental gene programmes in skin morphogenesis and during inflammatory disease could facilitate tissue engineering and novel treatment strategies.
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