Arthritis Rheumatol. 2026 Jan 12. doi: 10.1002/art.70051. Online ahead of print.
ABSTRACT
OBJECTIVES: This study investigated the role of IL-17 in Giant Cell Arteritis (GCA), which has remained uncertain despite previous research suggesting a contribution of Th17 cells to the disease.
METHODS: Temporal artery biopsies (TABs) were cultured ex vivo in MATRIGEL® with IL-17, secukinumab, or control IgG, and subsequently analyzed using bulk RNA-sequencing and RT-qPCR. Positive-TABs with GCA features were compared to negative-TABs or used to obtain in vitro cultures of myofibroblasts (MFs). Confocal microscopy analyzed IL-17 receptor expression. MFs and peripheral blood mononuclear cells co-cultures were used to study T-cell polarization.
RESULTS: Transcriptomic analysis showed that secukinumab treatment of positive TABs reduced expression of genes linked to vascular inflammation, notably IL6. RT-qPCR analysis confirmed that secukinumab decreased mRNA encoding IL-6, CCL20, and GM-CSF in positive-TABs, while IL-17 upregulated them in negative-TABs. No changes were observed regarding the expression of genes related to vascular remodeling. IL-17 receptor chains were expressed on MFs, and their expression was enhanced by IFN-γ. RT-qPCR and Luminex® analyses confirmed IL-17-driven upregulation of IL-6, CCL20, CCL2, GM-CSF, and VEGF in MFs, which was reversed by secukinumab. Addition of IFN-γ to the culture increased the expression level of IL-17 receptor chains, resulting in a synergistic effect. Additionally, IL-17 pre-treated MFs promoted Th17 polarization.
CONCLUSIONS: IL-17 exacerbates vascular inflammation in GCA by activating MFs and synergizing with IFN-γ to increase production of pro-inflammatory cytokines (IL-6, GM-CSF), chemokines (CCL20, CCL2), and angiogenic factors (VEGF, indicating that IL-17 is a key contributor to disease pathogenesis.
PMID:41524618 | DOI:10.1002/art.70051