Activated B cells drive fibroblasts toward a pro-inflammatory phenotype, potentially sustaining chronic inflammation and disease progression in GCA, and JAK-STAT signalling appears central to this effect.
Distinct fibroblast subsets occupy different positions in and around CD20+ B cell clusters in GCA and atherosclerotic aortic tissue.
Fibroblasts in or around B cell clusters co-express the cytokines IL-6, GM-CSF and BAFF.
Human aortic adventitial fibroblasts (HAoAFs) cocultured with activated B cells, or their supernatants, upregulated pro-inflammatory and activation markers.
Fibroblasts exposed to activated B cells actively secreted IL-6, GM-CSF and BAFF while type I collagen expression was suppressed.
JAK-STAT inhibition abrogated the pro-inflammatory effects of activated B cell conditioned medium on fibroblasts, whereas TNF-α and IL-6 receptor blockade did not.
The authors conclude that B cell–fibroblast interactions may sustain chronic vascular inflammation in GCA and that JAK-STAT signalling is central, supporting therapeutic potential of JAK inhibition at the vascular level.
Giant cell arteritis (GCA) is a disease in which large arteries, especially the aorta, become chronically inflamed and remodelled. In affected artery walls, clusters of immune cells called B cells sit in the outer layer, where fibroblasts (structural cells) are the main cell type. This study examined which kinds of fibroblasts sit near these B cell clusters and how B cells and fibroblasts influence each other. In aortic tissue, different fibroblast types were arranged in distinct zones of the clusters, and fibroblasts in or around them produced inflammatory signals (IL-6, GM-CSF and BAFF). In laboratory experiments, aortic fibroblasts exposed to activated B cells, or to fluid from them, turned on inflammatory genes, released more inflammatory proteins and made less type I collagen. This suggests B cells can push fibroblasts into an inflammatory state that may help keep inflammation going. Blocking the JAK-STAT signalling pathway with the drugs baricitinib or upadacitinib prevented these changes, whereas blocking TNF-α or the IL-6 receptor did not. This research suggests JAK-STAT inhibitors might act on artery-wall inflammation in GCA, but the interaction experiments were done in cell cultures, so clinical benefit would need to be tested in patients.
Xu S, Jiemy W, Inrueangsri N, Ko Y, Abdulahad W, Verschoor E, et al.. (2026). Activated B cells steer fibroblasts towards a proinflammatory phenotype in giant cell arteritis.. Rheumatology (Oxford, England). https://doi.org/10.1093/rheumatology/keag563