FIGURE 5.

The NOTCH signaling pathway in giant cell arteritis. A signature abnormality of CD4⁺ T cells in GCA is the aberrant expression of the NOTCH1 receptor. NOTCH1⁺ CD4⁺ T cells engage the JAGGED1 ligand on the surface of microvascular endothelial cells. Vascular endothelial growth factor (VEGF) in the circulation functions as the JAGGED1 inducer. Via HES1, the NOTCH signaling pathway activates the mechanistic target of rapamycin complex 1 (mTORC1). Persistent NOTCH signaling promotes T cell proliferation, invasion of CD4⁺ T cells into the vessel wall, upregulation of the metabolic program and differentiation into cytokine-producing effector cells.