Activated B cells steer fibroblasts towards a proinflammatory phenotype in giant cell arteritis.
- 1Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
- 2Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
- 3Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, UAE.
Abstract
Objectives
Giant cell arteritis (GCA) is characterized by chronic large-vessel inflammation and remodelling. Within affected arteries, especially in aorta, organized B cell clusters are mainly localized in adventitia, where fibroblasts represent the dominant stromal population. This study aims to investigate fibroblast heterogeneity within these clusters and B cell-fibroblast interactions in vitro as possible contributors to disease chronicity in GCA.Methods
Fibroblast phenotypes in CD20+ B cell clusters in GCA and atherosclerotic aortic tissues were characterized using immunohistochemistry for fibroblast markers (CD90, podoplanin [PDPN], fibroblast activation protein [FAP], CD248, α-smooth muscle actin [α-SMA]) and cytokine expression (IL-6, GM-CSF, B-cell activating factor [BAFF]). In vitro, peripheral blood B cells from treatment-naïve GCA patients and healthy donors were stimulated and cocultured with human aortic adventitial fibroblasts (HAoAFs) using either direct cell coculture or transwell systems. To identify relevant molecular pathways for B cell-fibroblast interaction, HAoAFs were pre-treated with infliximab, tocilizumab, baricitinib or upadacitinib, followed by exposure to activated B cell conditioned medium. Protein secretion was assessed by ELISA, Luminex and Olink; mRNA expression was determined by qPCR.Results
CD90+PDPN+ immunofibroblasts mainly localized centrally, whereas CD90+FAP+ and CD90+CD248+ fibroblasts mostly located at the border of the clusters. Fibroblasts in or around clusters co-expressed IL-6, GM-CSF and BAFF. In vitro, HAoAFs cocultured with activated B cells or supernatants thereof upregulated IL-6, GM-CSF, PDPN and FAP mRNA, and actively secreted IL-6, GM-CSF and BAFF, while type I collagen expression was suppressed. Janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibition abrogated these pro-inflammatory effects, whereas TNF-α and IL-6 receptor blockade did not.Conclusion
Activated B cells drive fibroblasts toward a pro-inflammatory phenotype, potentially sustaining chronic inflammation and disease progression in GCA. JAK-STAT signalling appears central to this effect, highlighting its therapeutic potency at the vascular level in GCA.
Related
- TRPC1 Promotes Thoracic Aortic Dissection Through Inducing Proinflammatory Phenotype of Vascular Smooth Muscle Cells
- Ciprofloxacin-Induced Oxidative Stress Promotes a Senescence-like Phenotype in Human Fibroblasts In Vitro.
- The mechanism of NaB-activated lytic replication of EBV and its hub genes in transcriptome regulation of gastric cancer cells
- Prednisolone attenuates the immunomodulatory capacity and reshapes the functional phenotype of canine adipose-derived mesenchymal stromal cells
- LncRNA FGD5-AS1 promotes M2 polarization of tumor-associated macrophages to facilitate the malignant phenotype of non-small cell lung cancer cells
BibTeX
@article{xu2026activated,
title = {{Activated B cells steer fibroblasts towards a proinflammatory phenotype in giant cell arteritis.}},
author = {Shuang Xu and William F Jiemy and Nanthicha Inrueangsri and YouBeen Ko and Wayel H Abdulahad and Ellen Verschoor and Yannick van Sleen and Jacoba C Graver and Kornelis S M van der Geest and Gwenny M Verstappen and Elisabeth Brouwer and Peter Heeringa and Annemieke M H Boots and Maria Sandovici},
journal = {Rheumatology (Oxford, England)},
year = {2026},
month = oct,
doi = {10.1093/rheumatology/keag563},
url = {https://europepmc.org/article/MED/42897993},
note = {CC BY},
}
RIS
TY - JOUR
TI - Activated B cells steer fibroblasts towards a proinflammatory phenotype in giant cell arteritis.
AU - Shuang Xu
AU - William F Jiemy
AU - Nanthicha Inrueangsri
AU - YouBeen Ko
AU - Wayel H Abdulahad
AU - Ellen Verschoor
AU - Yannick van Sleen
AU - Jacoba C Graver
AU - Kornelis S M van der Geest
AU - Gwenny M Verstappen
AU - Elisabeth Brouwer
AU - Peter Heeringa
AU - Annemieke M H Boots
AU - Maria Sandovici
PY - 2026
DA - 2026/10/01
JO - Rheumatology (Oxford, England)
DO - 10.1093/rheumatology/keag563
UR - https://europepmc.org/article/MED/42897993
AB - Objectives Giant cell arteritis (GCA) is characterized by chronic large-vessel inflammation and remodelling. Within affected arteries, especially in aorta, organized B cell clusters are mainly localized in adventitia, where fibroblasts represent the dominant stromal population. This study aims to investigate fibroblast heterogeneity within these clusters and B cell-fibroblast interactions in vitro as possible contributors to disease chronicity in GCA.Methods Fibroblast phenotypes in CD20+ B cell clusters in GCA and atherosclerotic aortic tissues were characterized using immunohistochemistry for fibroblast markers (CD90, podoplanin [PDPN], fibroblast activation protein [FAP], CD248, α-smooth muscle actin [α-SMA]) and cytokine expression (IL-6, GM-CSF, B-cell activating factor [BAFF]). In vitro, peripheral blood B cells from treatment-naïve GCA patients and healthy donors were stimulated and cocultured with human aortic adventitial fibroblasts (HAoAFs) using either direct cell coculture or transwell systems. To identify relevant molecular pathways for B cell-fibroblast interaction, HAoAFs were pre-treated with infliximab, tocilizumab, baricitinib or upadacitinib, followed by exposure to activated B cell conditioned medium. Protein secretion was assessed by ELISA, Luminex and Olink; mRNA expression was determined by qPCR.Results CD90+PDPN+ immunofibroblasts mainly localized centrally, whereas CD90+FAP+ and CD90+CD248+ fibroblasts mostly located at the border of the clusters. Fibroblasts in or around clusters co-expressed IL-6, GM-CSF and BAFF. In vitro, HAoAFs cocultured with activated B cells or supernatants thereof upregulated IL-6, GM-CSF, PDPN and FAP mRNA, and actively secreted IL-6, GM-CSF and BAFF, while type I collagen expression was suppressed. Janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibition abrogated these pro-inflammatory effects, whereas TNF-α and IL-6 receptor blockade did not.Conclusion Activated B cells drive fibroblasts toward a pro-inflammatory phenotype, potentially sustaining chronic inflammation and disease progression in GCA. JAK-STAT signalling appears central to this effect, highlighting its therapeutic potency at the vascular level in GCA.
SN - 1462-0324
SN - 1462-0332
ER -