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Home»News»Mettl3 directs CD8 T cells to eliminate infected cells with maximal efficiency
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Mettl3 directs CD8 T cells to eliminate infected cells with maximal efficiency

healthtostBy healthtostDecember 30, 2023No Comments2 Mins Read
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Mettl3 Directs Cd8 T Cells To Eliminate Infected Cells With
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December 29, 2023

This study is led by Dr. Shuyang Yu (College of Biological Sciences, China Agricultural University), Dr. Jingyu Xu (Collaborative Center for Tissue Damage Repair and Regenerative Medicine, Zunyi Medical University) and Dr. Xuguang Du (College of Biological Sciences, China Agricultural University) and illustrated the key role of Mettl3 in the CD8 T cell response during the acute model contamination.

CD8 T cells (also known as cytotoxic T cells) are a key component of the adaptive immune system. Once activated upon contact with antigens, naïve CD8 T cells undergo a rapid proliferative expansion and differentiate into effector and memory cells, which enhance host defense by eliminating foreign pathogens. With the development of RNA biology, the functions of N6-methyladenosine (m6A) in various cell subsets have been widely reported, while the CD8 T cell response is less reported. This study highlighted the key role of m6A modifies and clarified the mechanisms of m6A modification in the regulation of the CD8 T cell response.

Scientists used in vivo infection models and adoptive transfer systems to reveal the essential role of Mettl3 during the CD8 T cell response. The results showed that the rate of early proliferation is reduced and apoptosis is increased, which leads to defective clonal expansion of CD8 T cells. Furthermore, the number of all effector subsets is severely impaired although the percentage of short-lived effector cells (SLEC) is reduced while memory progenitor effector cells (MPEC) are relatively increased in Mettl3-deficient CD8 T cells. Meanwhile, Mettl3-deficient CD8 T cells have significantly reduced memory formation and secondary response capacity.

To examine Mettl3-dependent epi-transcriptional regulation in effector CD8 T cells, this study combined the transcriptional and m6An abundance modification analysis of effector CD8 T cells. The scientists revealed that the Mettl3-dependent m6A modification regulates the expression of genes related to the cell cycle and differentiation. Specifically, the Mettl3-mediated m6A modification is binding Tbx21 transcription and maintains its stability, allowing normal production of the T-bet protein. Ectopic expression of T-bet primarily restores the phenotypic defects in SLEC and MPEC differentiation of Mettl3-deficient CD8 T cells. In summary, this study demonstrated that the Mettl3-dependent m6A modification modulates the CD8 T cell response during the acute infection process.

Source:

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CD8 cells directs efficiency eliminate infected maximal Mettl3
bhanuprakash.cg
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