Abstract
T cells play pivotal roles in inflammation's initiation and progression. Exploring natural compounds that regulate T cell function is crucial for preventing and treating inflammation. Herein, we report that Alternariol (AOH), a marine-derived secondary metabolite, exerts an anti-inflammatory activity by targeting T cell function. Using an ovalbumin (OVA)-induced OT-II CD4+ T cell activation model, we demonstrated that AOH potently suppresses T cell proliferation and cytokine secretion, mildly promotes T cell apoptosis, and spares antigen presentation processes. Mechanistically, AOH controlled early T cell activation by inhibiting the expression of activation markers (CD69, CD25, CD44) and transcription factors (T-bet, Eomes), leading to impaired Th1 cytokine production. In vivo experiments revealed that AOH attenuated OVA-induced lung injury in mice by reducing immune cell infiltration in pulmonary tissues and draining lymph nodes. Notably, AOH dramatically suppressed OVA-specific T cells migrating to the inflammatory lung while impairing T-cell-mediated other immune cell infiltration. Collectively, AOH exhibited potent anti-inflammatory effects by modulating T cell proliferation, function, and migration, offering a promising therapeutic strategy for T-cell-mediated inflammatory diseases.