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BACKGROUND: double negative T regulatory cells (DNT) decrease cell survival and immunosuppressive function, leading to aggravated liver inflammation. In this study, we aim to reveal the underlying mechanisms that cause changes in DNT during MASLD progression. METHODS: The correlation of serum oxidized low-density lipoprotein (oxLDL) levels and DNT from patients with MASLD and MASLD mouse models were evaluated. The mechanisms of oxLDL affecting DNT survival and function were explored through transcriptome sequencing analysis, flow cytometry, and CUT & TAG experiments. RESULTS: DNT compared to wild type DNT. This improvement in DNT results in a notable enhancement of therapeutic efficacy against MASLD. CONCLUSION: oxLDL induces a decline in the survival and immune regulatory function of DNT, subsequently weakening their role in maintaining liver immune homeostasis in MASLD. Specific targeting of CD36 to prevent ferroptosis in DNT may provide a novel therapeutic approach for the treatment of MASLD.
Wei et al. (Mon,) studied this question.