Integrated transcriptomic and functional analyses identify LAIR1 as a key immunoregulatory molecule in postoperative sepsis
- 1Department of Anesthesiology, The Second Xiangya Hospital, Central South University
- 2Anesthesiology Research Institute, Central South University
Abstract
Background: Postoperative sepsis arises from a dysregulated host response to infection following surgical stress. Current non-specific biomarkers offer insufficient predictive value, highlighting the need to identify molecular signatures that may facilitate earlier recognition of postoperative sepsis while providing insight into the underlying immune regulatory mechanisms.
Methods: Transcriptomic datasets comprising postoperative septic and non-septic surgical cohorts, together with independent cohorts of sepsis and non-infectious systemic inflammation, were analyzed using Weighted Gene Co-expression Network Analysis and machine-learning approaches to identify hub genes. A diagnostic nomogram was constructed and validated across independent cohorts. A murine postoperative endotoxemia model (tibial fracture surgery followed by LPS challenge) was used for in vivo validation. Single-cell RNA sequencing analysis and LAIR1 antibody blockade were performed to assess cellular and functional relevance.
Results: A four-gene signature comprising LAIR1, PLAC8, ACSS2, and PCOLCE2 was identified. The resulting model achieved AUCs of 0.865 in GSE131761, 0.965 in GSE74224, 0.827 in E-MTAB-1548, 0.929 in GSE65682, and 0.997 in GSE77167. Among the four genes, LAIR1 showed the most sustained upregulation in peripheral blood and multiple organs during postoperative endotoxemia. Single-cell analysis identified monocytes as the predominant circulating source of LAIR1. LAIR1 blockade increased systemic cytokine release, aggravated multiorgan injury, and reduced survival.
Conclusions: The four-gene signature reproducibly distinguished sepsis from infection-negative systemic inflammation across surgical and broader ICU cohorts. LAIR1 exhibited monocyte-enriched expression and a protective immunoregulatory role in postoperative endotoxemia, supporting its relevance to immune dysregulation of sepsis.
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BibTeX
@article{liu2026integrated,
title = {{Integrated transcriptomic and functional analyses identify LAIR1 as a key immunoregulatory molecule in postoperative sepsis}},
author = {Tao Liu and Yang Wang and Liyun Zeng and Xuemei Miao and Yu Peng and Jingying Yu and Jiaying Li and Qian Zhao and Ziyan Chen and Ruping Dai and Hui Li},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1931628},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1931628/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrated transcriptomic and functional analyses identify LAIR1 as a key immunoregulatory molecule in postoperative sepsis
AU - Tao Liu
AU - Yang Wang
AU - Liyun Zeng
AU - Xuemei Miao
AU - Yu Peng
AU - Jingying Yu
AU - Jiaying Li
AU - Qian Zhao
AU - Ziyan Chen
AU - Ruping Dai
AU - Hui Li
PY - 2026
DA - 2026/10/14
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1931628
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1931628/full
AB - Background: Postoperative sepsis arises from a dysregulated host response to infection following surgical stress. Current non-specific biomarkers offer insufficient predictive value, highlighting the need to identify molecular signatures that may facilitate earlier recognition of postoperative sepsis while providing insight into the underlying immune regulatory mechanisms. Methods: Transcriptomic datasets comprising postoperative septic and non-septic surgical cohorts, together with independent cohorts of sepsis and non-infectious systemic inflammation, were analyzed using Weighted Gene Co-expression Network Analysis and machine-learning approaches to identify hub genes. A diagnostic nomogram was constructed and validated across independent cohorts. A murine postoperative endotoxemia model (tibial fracture surgery followed by LPS challenge) was used for in vivo validation. Single-cell RNA sequencing analysis and LAIR1 antibody blockade were performed to assess cellular and functional relevance. Results: A four-gene signature comprising LAIR1, PLAC8, ACSS2, and PCOLCE2 was identified. The resulting model achieved AUCs of 0.865 in GSE131761, 0.965 in GSE74224, 0.827 in E-MTAB-1548, 0.929 in GSE65682, and 0.997 in GSE77167. Among the four genes, LAIR1 showed the most sustained upregulation in peripheral blood and multiple organs during postoperative endotoxemia. Single-cell analysis identified monocytes as the predominant circulating source of LAIR1. LAIR1 blockade increased systemic cytokine release, aggravated multiorgan injury, and reduced survival. Conclusions: The four-gene signature reproducibly distinguished sepsis from infection-negative systemic inflammation across surgical and broader ICU cohorts. LAIR1 exhibited monocyte-enriched expression and a protective immunoregulatory role in postoperative endotoxemia, supporting its relevance to immune dysregulation of sepsis.
SN - 1664-3224
ER -