Objectives: Takayasu's arteritis (TAK) is a progressive autoimmune vasculitis that mainly affects the aorta and its major branches. While recent studies have identified proinflammatory T cells, including Th1 and Th17 cells, as the dominant infiltrates in the arterial adventitia, mechanisms underpinning the maintenance of such vasculogenic T cells remain obscure.
Methods: 75 patients with TAK and 30 age-matched healthy controls were enrolled in this study. CD4 T cells from TAK patients were activated with anti-CD3/CD28 beads to mimic vasculogenic T cells. The survival of T cells was detected by quantifying Annexin-V+7-AAD+ fractions. Expression and activity of AMP-activated protein kinase (AMPK) were determined using phosflow cytometry and immunoblots. Specific inhibitors and shRNA were applied to block the function of AMPK and Notch1, while erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to reflect the disease activity of TAK patients.
Results: T cells from TAK patients undergo spontaneous differentiation into vasculogenic proinflammatory T cells with prolonged survival capacity. Mechanistic explorations uncover AMPK hyperactivity in such T cells from TAK patients, promoting mitochondrial metabolism and their survival. Such AMPK hyperactivity results from the robust Notch1 activity in TAK T cells. Accordingly, T cell-intrinsic phosphor-AMPK reflects the disease activity in clinical TAK patients.
Conclusions: AMPK hyperactivity is essential for maintaining the vasculogenic proinflammatory T cells in TAK patients, serving as a promising therapeutic target for TAK management.