Single-Cell Analysis Reveals Major Histocompatibility Complex II‒Expressing Keratinocytes in Pressure Ulcers with Worse Healing Outcomes
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Single-Cell Analysis Reveals Major Histocompatibility Complex II‒Expressing Keratinocytes in Pressure Ulcers with Worse Healing Outcomes. / Li, Dongqing; Cheng, Shangli; Pei, Yu; Sommar, Pehr; Kärner, Jaanika; Herter, Eva K.; Toma, Maria A.; Zhang, Letian; Pham, Kim; Cheung, Yuen Ting; Liu, Zhuang; Chen, Xingqi; Eidsmo, Liv; Deng, Qiaolin; Xu Landén, Ning.
In: Journal of Investigative Dermatology, Vol. 142, No. 3, Part A, 2022, p. 705-716.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Single-Cell Analysis Reveals Major Histocompatibility Complex II‒Expressing Keratinocytes in Pressure Ulcers with Worse Healing Outcomes
AU - Li, Dongqing
AU - Cheng, Shangli
AU - Pei, Yu
AU - Sommar, Pehr
AU - Kärner, Jaanika
AU - Herter, Eva K.
AU - Toma, Maria A.
AU - Zhang, Letian
AU - Pham, Kim
AU - Cheung, Yuen Ting
AU - Liu, Zhuang
AU - Chen, Xingqi
AU - Eidsmo, Liv
AU - Deng, Qiaolin
AU - Xu Landén, Ning
N1 - Publisher Copyright: © 2021 The Authors
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1016/j.jid.2021.07.176
DO - 10.1016/j.jid.2021.07.176
M3 - Journal article
C2 - 34536485
AN - SCOPUS:85116880262
VL - 142
SP - 705
EP - 716
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 3, Part A
ER -
ID: 283139463