Cholesterol metabolism in immune cells: From mechanisms to therapeutic opportunities

All immune cells engage in cholesterol metabolism, which generates a spectrum of bioactive metabolites that mainly include cholesterol itself, its biosynthetic intermediates, and oxidized or sulfated derivatives. These metabolites regulate not only cellular metabolism but also immune signaling. In addition, several functional proteins within cholesterol metabolic pathways exert non-canonical signaling functions that shape immune cell responses. Distinct immune cell types adopt specialized cholesterol metabolic programs tailored to their functional demands, and these programs are further influenced by physiological factors such as diet and aging. In human disease, immune cell cholesterol metabolism is frequently dysregulated, which highlights metabolic intervention as a promising therapeutic strategy. Accordingly, the repurposing of established metabolic drugs such as statins and PCSK9 inhibitors is gaining momentum, alongside the identification of additional therapeutic targets. A deeper understanding of how cholesterol metabolism governs immune responses will advance fundamental immunology and accelerate the development of next-generation immunotherapies.