Home Medizin Mettl3 leitet CD8-T-Zellen an, infizierte Zellen mit maximaler Effizienz zu eliminieren

Mettl3 leitet CD8-T-Zellen an, infizierte Zellen mit maximaler Effizienz zu eliminieren

von NFI Redaktion


This study was conducted by Dr. Shuyang Yu (College of Biological Sciences, China Agricultural University), Dr. Jingyu Xu (The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine at Zunyi Medical University), and Dr. Sciences, China Agricultural University, and illustrated the key role of Mettl3 in the CD8-T cell response in an acute infection model.

CD8 T cells (also known as cytotoxic T lymphocytes) are a key component of the adaptive immune system. After activation upon encountering antigens, naive CD8 T cells rapidly proliferate and differentiate into effector and memory cells that enhance organism protection by removing foreign pathogens. With the advancement of RNA biology, the functions of N6-methyladenosine (m6A) in various cell subsets have been widely reported, while less has been reported on the CD8-T cell response. This study emphasized the key role of m6A modification and elucidated the mechanisms of m6A modification in regulating the CD8-T cell response.

The scientists used in vivo infection models and adoptive transfer systems to uncover the key role of Mettl3 during the CD8-T cell response. The results showed that the rate of early proliferation is decreased and apoptosis is increased, leading to faulty clonal expansion of CD8-T cells. Additionally, the number of all effector subsets is greatly impaired, although the proportion of short-lived effector cells (SLEC) is reduced, while memory precursor effector cells (MPEC) in Mettl3-deficient CD8-T cells are relatively increased. Meanwhile, Mettl3-deficient CD8-T cells significantly impair the ability for memory formation and secondary response.

To examine the Mettl3-dependent epitranscriptional regulation in effector CD8-T cells, this study combined transcriptome and m6A modification frequency analysis of effector CD8-T cells. The scientists showed that Mettl3-dependent m6A modification regulates the expression of cell cycle- and differentiation-related genes. Specifically, Mettl3-mediated m6A modification binds to the Tbx21 transcript and maintains its stability, allowing for normal production of T-bet protein. Ectopic expression of T-bet mainly restores the phenotypic defects in SLEC and MPEC differentiation of Mettl3-deficient CD8-T cells. In summary, this study demonstrated that Mettl3-dependent m6A modification regulates the CD8-T cell response during the acute infection process.

Quelle:

Zeitschriftenreferenz:

Guo, W., et al. (2023). Die Mettl3-abhängige m6A-Modifikation ist für die Effektordifferenzierung und Gedächtnisbildung von CD8+ T-Zellen essentiell. Wissenschaftsbulletin. doi.org/10.1016/j.scib.2023.11.029.

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