Identification of BHLHE40-expressing T cells in giant cell arteritis amplified by interleukin-1.

BHLHE40 is a transcription factor regulating proinflammatory cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) in CD4+ T cells. Although implicated in autoimmune inflammation, its regulation by interleukin (IL)-1 signaling in human CD4+ T cells remains unclear. Peripheral blood (PB) from healthy controls (HCs) and patients with giant cell arteritis (GCA) was analyzed using flow cytometry to assess BHLHE40 expression across helper T cells. Immunohistochemistry was performed on the aortas of IL-1 receptor antagonist knockout (IL-1Rn KO) mice and temporal artery biopsies from GCA patients. We also analyzed public microarray datasets and CD4+ T cells stimulated with anti-CD3/CD28 and IL-1β. We identified BHLHE40 expression in T cells in the IL-1Rn KO mice and GCA-inflamed arteries. BHLHE40 expression was higher in helper T subsets than in naïve CD4+ T cells. Co-stimulation with IL-1β and anti-CD3/CD28 induced stronger BHLHE40 expression than CD3/CD28 alone. Microarray data showed increased expression of BHLHE40 in CD4+ T cells from the PB of GCA patients. IL-1 signaling enhances BHLHE40 expression during CD4+ T cell activation. Its sustained expression in inflamed tissues suggests a disease-relevant pathway linking IL-1 signaling to pathogenic T cell responses in GCA.