Rheumatology (Oxford, England) · 2026
Activated B cells steer fibroblasts towards a proinflammatory phenotype in giant cell arteritis.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Xu Shuang, Jiemy William F, Inrueangsri Nanthicha, Ko YouBeen, Abdulahad Wayel H, Verschoor Ellen, van Sleen Yannick, Graver Jacoba C, van der Geest Kornelis S M, Verstappen Gwenny M, Brouwer Elisabeth, Heeringa Peter, Boots Annemieke M H, Sandovici Maria
Аннотация
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, PDPN, FAP, CD248, α-SMA) and cytokine expression (IL-6, GM-CSF, 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 (aBCCM). 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/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. 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.
METHODS: Fibroblast phenotypes in CD20+B cell clusters in GCA and atherosclerotic aortic tissues were characterized using immunohistochemistry for fibroblast markers (CD90, PDPN, FAP, CD248, α-SMA) and cytokine expression (IL-6, GM-CSF, 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 (aBCCM). 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/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. 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.