Usage Information
Abstract
Giant cell aortitis (GCA) is an inflammatory disease of the aortic wall with a characteristic giant cell pattern on pathology and can lead to life-threatening aortic aneurysm and dissection. Pathogenic GCA mechanisms underlying aortic inflammation and persistence remain elusive. Here, we demonstrate the complexity of medial layer destruction and immune cell infiltration in clinical granulomatous GCA and lymphoplasmacytic IgG4-related aortitis samples using imaging-based gene expression profiling. Single-cell spatial profiling revealed aortic wall remodeling in the GCA aortas, highlighting substantial phenotypic modulation in stromal cells, including vascular smooth muscle cells (SMCs) and fibroblasts. Specifically, we observed the expansion of stromal cells expressing Tenascin-C (TNC) mRNA and spatially refined TNC accumulation in lesion areas. We confirmed these findings histologically using diseased aortas resected from individuals with giant cell arteritis and clinically isolated aortitis. Mechanistically, our data suggest that TNC promotes a proinflammatory phenotype in primary human SMCs, elevating IL-6 levels partially through the TLR4/NF-κB pathway. IL-6 signaling propagates the proinflammatory loop by activating STAT3. Pharmacological blockade of the IL-6 receptor using tocilizumab alleviated the TNC-driven proinflammatory phenotype. We propose that TNC acts as a local catalyst of inflammatory disease persistence mainly via IL-6 signaling activation and offers a potential avenue for sustained disease remission.
Authors
Hui Shi, Ying Tang, Jing Li, Ora Gewurz-Singer, Bo Yang, Dogukan Mizrak
Usage data is cumulative from April 2026 through May 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 848 | 0 |
| 207 | 0 | |
| Figure | 235 | 0 |
| Supplemental data | 195 | 0 |
| Citation downloads | 82 | 0 |
| Totals | 1,567 | 0 |
| Total Views | 1,567 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
