| Title: | Bilirubin mitigates ischemic white matter injury by targeting transferrin-receptor-mediated B cell immunometabolism |
| Journal: | Cell Reports |
| Published: | 9 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42268716/ |
| DOI: | https://doi.org/10.1016/j.celrep.2026.117398 |
Publication 20755
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Abstract
Physiological bilirubin exerts protective effects against ischemic stroke, but its role in post-stroke white matter injury (WMI) remains unclear. Here, through integrated epidemiological, genetic, and mechanistic studies, we demonstrate that mild elevation of serum bilirubin mitigates ischemic WMI by modulating B cell immunometabolism. Prospective cohort and Mendelian randomization analyses revealed an inverse association between bilirubin levels and WMI severity. In experimental models, bilirubin suppressed B cell activation and neuroinflammation by targeting transferrin receptor (TFRC), thereby reducing iron overload, restoring glucose metabolism, and improving mitochondrial homeostasis. Single-cell profiling further linked bilirubin-mediated B cell modulation to attenuated microglial activation via Fcγ receptor signaling. The existence of a bilirubin-B cell immunometabolism axis bridges preclinical findings with clinical relevance. Our findings establish bilirubin as a key immunometabolic checkpoint in B cells and propose TFRC blocking as a therapeutic strategy for ischemic WMI.</p>
10 Keywords
- Animals
- B-Lymphocytes
- Bilirubin
- Brain Ischemia
- Humans
- Male
- Mice
- Mice, Inbred C57BL
- Receptors, Transferrin
- White Matter
16 Authors
- Lian Chen
- Xiao-Wei Pang
- Zhi-Cheng Mei
- Lan Zhang
- Yun-Hui Chu
- Meng-Lu Tian
- Li-Fang Zhu
- Luo-Qi Zhou
- Sheng Yang
- Ming-Hao Dong
- Ke Shang
- Jun Xiao
- Jian-Ke Gong
- Wei Wang
- Dai-Shi Tian
- Chuan Qin
1 Application
| Application ID | Title |
|---|---|
| 94533 | A Study of risk factors for cardiovascular and cerebrovascular diseases |
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