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Research Paper|Volume 15, Issue 24|pp 14803—14829

Investigating the ID3/SLC22A4 as immune-related signatures in ischemic stroke

Dading Lu1,2,3, Heng Cai4, Yugang Li1, Wenyuan Chang2, Xiu Liu5, Qiwei Dai4, Wanning Yu4, Wangli Chen4, Guomin Qiao4, Haojie Xie4, Xiong Xiao4, Zhiqing Li1,2,3
  • 1Department of Stroke Center, The First Hospital of China Medical University, Heping, Shenyang, Liaoning, China
  • 2Department of Neurology, The First Hospital of China Medical University, Heping, Shenyang, Liaoning, China
  • 3Department of Neurosurgery, The First Hospital of China Medical University, Heping, Shenyang, Liaoning, China
  • 4Department of Neurosurgery, Shengjing Hospital, Shenyang, China medical University, Heping, Shenyang, China
  • 5The First Clinical College, China Medical University, Shenbei, Shenyang, China
Received: August 3, 2023Accepted: November 3, 2023Published: December 14, 2023
https://doi.org/10.18632/aging.205308

Copyright: © 2023 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Ischemic stroke (IS) is a fearful disease that can cause a variety of immune events. Nevertheless, precise immune-related mechanisms have yet to be systematically elucidated. This study aimed to identify immune-related signatures using machine learning and to validate them with animal experiments and single cell analysis.

Methods: In this study, we screened 24 differentially expressed genes (DEGs) while identifying immune-related signatures that may play a key role in IS development through a comprehensive strategy between least absolute shrinkage and selection operation (LASSO) regression, support vector machine (SVM) and immune-related genes. In addition, we explored immune infiltration using the CIBERSORT algorithm. Finally, we performed validation in mouse brain tissue and single cell analysis.

Results: We identified 24 DEGs for follow-up analysis. ID3 and SLC22A4 were finally identified as the better immune-related signatures through a comprehensive strategy among DEGs, LASSO, SVM and immune-related genes. RT-qPCR, western blot, and immunofluorescence revealed a significant decrease in ID3 and a significant increase in SLC22A4 in the middle cerebral artery occlusion group. Single cell analysis revealed that ID3 was mainly concentrated in endothelial_2 cells and SLC22A4 in astrocytes in the MCAO group. A CIBERSORT finds significantly altered levels of immune infiltration in IS patients.

Conclusions: This study focused on immune-related signatures after stroke and ID3 and SLC22A4 may be new therapeutic targets to promote functional recovery after stroke. Furthermore, the association of ID3 and SLC22A4 with immune cells may be a new direction for post-stroke immunotherapy.