SELL Marks an Effector-Deficient CD8<sup>+</sup> T Cell Subset That Promotes Intracerebral Hemorrhage and Responds to Rutin Therapy.

Overview

1. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, cacms.ac.cn
2. Department of Clinical Laboratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi′an, China, fmmu.edu.cn
3. National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine, Fuwai Central-China Hospital, Central-China Branch of the National Center for Cardiovascular Diseases, Zhengzhou, China
4. Institute of Cardiovascular Disease, Henan Academy of Innovations in Medical Science, Zhengzhou, China

Abstract

Background: Intracerebral hemorrhage (ICH) is a devastating stroke subtype with high mortality and limited therapeutic options. While neuroinflammation contributes to secondary brain injury, the role of peripheral CD8+ T cell dysfunction in ICH pathogenesis remains poorly characterized. This study is aimed at identifying disease‐associated CD8+ T cell subpopulations and potential therapeutic targets through integrative multiomics analysis.

Methods: We performed bulk RNA sequencing on peripheral blood from 130 patients (66 ICH and 64 hypertension controls) across two independent cohorts, combined with single‐cell RNA sequencing of 13 patients. The scPAS algorithm integrated bulk and single‐cell data to identify phenotype‐associated cells. Five machine learning algorithms (LASSO, random forest, XGBoost, SVM, and Boruta) were employed for biomarker discovery. The therapeutic efficacy of rutin was evaluated in murine hypertensive ICH models.

Results: We identified a distinct SELL‐high CD8+ T cell subpopulation (scPAS+ cells) exhibiting comprehensive effector dysfunction, characterized by downregulation of cytotoxicity genes (GZMA, GZMB, GNLY, NKG7, and CCL5). Pseudotime trajectory analysis revealed progressive differentiation toward this dysfunctional phenotype. SELL emerged as a consensus diagnostic biomarker across all five algorithms, demonstrating excellent discriminative performance (AUC: 0.876–0.936). In vivo, rutin treatment reduced SELL expression, restored CD8+ T cell cytotoxicity, decreased hemorrhage incidence, and attenuated neuroinflammation and oxidative stress.

Conclusions: This study identifies SELL‐marked effector‐deficient CD8+ T cells as a hallmark of ICH and establishes SELL as a robust diagnostic biomarker. Rutin represents a promising therapeutic candidate targeting peripheral immune dysfunction in hypertensive ICH.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• alphafold.ebi.ac.uk/entry/af-p14151-f1, at EMBL-EBI; found in the text, “2.7. Computational Docking Analysis”

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 2, 28 September 2026

• Issue: n/a → 1

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 6 authors, 7 keywords, 12 MeSH terms, 4 funders, 53 references.

Cite

This paper

Huang, Y., Xu, H., Bai, C., Liu, J., Sun, Y., & Chen, J. (2026). SELL Marks an Effector-Deficient CD8<sup>+</sup> T Cell Subset That Promotes Intracerebral Hemorrhage and Responds to Rutin Therapy. Human mutation, 2026(1), 4033506. https://doi.org/10.1155/humu/4033506

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