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Single-Cell Analysis Reveals Major Histocompatibility Complex II-Expressing Keratinocytes in Pressure Ulcers with Worse Healing Outcomes
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- Li, Dongqing (author)
- Karolinska Inst, Ctr Mol Med, Dept Med Solna, Dermatol & Venereol Div, Stockholm, Sweden.
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- Cheng, Shangli (author)
- Karolinska Inst, Ctr Mol Med, Dept Physiol & Pharmacol, Stockholm, Sweden.;Karolinska Inst, Ming Wai Lau Ctr Reparat Med, Stockholm, Sweden.
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- Pei, Yu (author)
- Karolinska Inst, Ctr Mol Med, Dept Physiol & Pharmacol, Stockholm, Sweden.
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- Karolinska Inst, Ctr Mol Med, Dept Med Solna, Dermatol & Venereol Div, Stockholm, Sweden Karolinska Inst, Ctr Mol Med, Dept Physiol & Pharmacol, Stockholm, Sweden.;Karolinska Inst, Ming Wai Lau Ctr Reparat Med, Stockholm, Sweden. (creator_code:org_t)
- Elsevier, 2022
- 2022
- English.
- In: Journal of Investigative Dermatology. - : Elsevier. - 0022-202X .- 1523-1747. ; 142:3, s. 705-716
- Journal article (peer-reviewed)
Abstract
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- 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-gamma 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)
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- art (subject category)
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- Li, Dongqing
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- Pei, Yu
- Sommar, Pehr
- Karner, Jaanika
- Herter, Eva K.
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- Zhang, Letian
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- Liu, Zhuang
- Chen, Xingqi
- Eidsmo, Liv
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- Landen, Ning Xu
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