640 Single-cell transcriptomics of human pressure ulcers reveals MHCII expressing keratinocytes in patients with a worse healing outcome

Abstract

Pressure ulcer (PU) is a chronic non-healing wound caused by continuous pressure of the bodyweight to the skin, which is often seen in spinal cord injury patients and the bedridden elderly population. Despite high mortality, the pathophysiology of PU remains poorly understood. Here we compared single-cell transcriptomic profiles on human epidermal cells from PU wound-edges with uninjured skin and acute wounds (AW) from healthy donors. We identified significant shifts of cellular composition and gene expression pattern in PU wound-edges, which could stratify PU into two groups. Interestingly, our study identified a subset of keratinocytes expressing major histocompatibility complex class II (MHCII), and these cells are enriched in patients with worse healing outcomes. We showed that IFNg in PU-derived wound fluid could induce MHCII expression in keratinocytes, and these wound fluid-treated keratinocytes inhibit autologous T cell activation. In line with this, we found that T cells from PUs enriched with MHCII+ keratinocytes produced less inflammatory cytokines. Together, our study provides a high-resolution molecular map of human PU compared to AW and the skin, which sheds new insights into the understanding of PU pathology and the future development of tailored wound therapy.