Abstract
Pressure ulcer (PU) is a chronic wound often seen in patients with spinal cord injury and other bed-bound individuals, particularly in the elderly population. Despite its association with high mortality, the pathophysiology of PU remains poorly understood. In this study, we compared single-cell transcriptomic profiles of human epidermal cells from PU wound edges with those from uninjured skin and acute wounds in healthy donors. We identified significant shifts in the cell composition and gene expression patterns in PU. In particular, we found that major histocompatibility complex class II‒expressing keratinocytes were enriched in patients with worse healing outcomes. Furthermore, we showed that the IFN-γ in PU-derived wound fluid could induce major histocompatibility complex II expression in keratinocytes and that these wound fluid‒treated keratinocytes inhibited autologous T-cell activation. In line with this observation, we found that T cells from PUs enriched with major histocompatibility complex II+ keratinocytes produced fewer inflammatory cytokines. Overall, our study provides a high-resolution molecular map of human PU compared with that of acute wounds and intact skin, providing insights into PU pathology and the future development of tailored wound therapy.
Highlights
A pressure ulcer (PU) is a chronic nonhealing wound that is caused by the continuous pressure of the bodyweight on the skin
Among the many previously unknown or poorly characterized cellular and molecular events uncovered by this scRNA-seq analysis, we focused on a subset of keratinocytes (KCs) expressing major histocompatibility complex (MHC) class II because they were enriched in Pressure ulcer (PU) with worse healing outcomes after reconstructive surgery
We collected uninjured skin and day-7 acute wound (AW) from four healthy donors who were matched to these patients with PU in terms of age, sex, ethnicity, and body location (Figure 1a and Supplementary Figure S1 and Supplementary Table S1)
Summary
A pressure ulcer (PU) is a chronic nonhealing wound that is caused by the continuous pressure of the bodyweight on the skin. PUs are often seen in patients with spinal cord injury and among bed-bound individuals, especially in the elderly population (Hajhosseini et al, 2020). Most patients with PU receive conservative treatment consisting of pressure relief and dressing changes, which can last for months to years. A minority of patients with PU receive reconstructive surgery with resection of the wound and flap coverage of the defect after the failure of conservative therapy. This is an extensive procedure and is unsuitable for elderly individuals and critically ill patients with multiple comorbidities (Hajhosseini et al, 2020). A deeper understanding of PU pathophysiology and the identification of therapeutic targets are pressing needs
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