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Tertiary Lymphoid Structures and CXCL13 as Targets in Intracranial Aneurysm
Zhiyao Zheng1,2,3, Zishuo Lu4, Ziliang Han2,3
1Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (Z.Z., N.W., X.Z., Y.W., W.M.).
Circulation Research
|July 21, 2026
Summary
Tertiary lymphoid structures and CXCL13+ T follicular helper cells drive intracranial aneurysm progression and rupture. Targeting the CXCL13 signaling pathway offers a promising therapeutic strategy for preventing aneurysm advancement.
Area of Science:
- Immunology
- Neuroscience
- Vascular Biology
Background:
- Intracranial aneurysms (IAs) are arterial dilations posing a rupture risk, causing subarachnoid hemorrhage.
- Immune cell infiltration drives IA pathogenesis, but detailed immune cell composition and spatial distribution are unclear.
Purpose of the Study:
- To comprehensively characterize the immune cell landscape and spatial architecture in human intracranial aneurysms.
- To identify key immune players and pathways involved in IA progression and rupture.
Main Methods:
- Integrated multi-omics approach: single-cell RNA sequencing, spatial transcriptomics, microarray, and multiplex immunofluorescence on human IA tissues.
- Validation in a mouse model of intracranial aneurysm.
Main Results:
- First identification of tertiary lymphoid structures (TLS) within the aneurysm wall, correlating strongly with rupture.
- Significant expansion of CXCL13+ T-follicular helper cells, crucial for B-cell recruitment and TLS organization.
- CXCL13 neutralization suppressed aneurysm formation and rupture in a mouse model.
Conclusions:
- Tertiary lymphoid structures and CXCL13+ T follicular helper cells are central to IA progression.
- The CXCL13 signaling axis represents a potential therapeutic target for preventing IA advancement.
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