Loss of YTHDF2 enhances Th9 programming and CAR-Th9 cell antitumor efficacy.

ABSTRACT: CD4⁺ T cells differentiate into various subsets, including T helper 1 (Th1), Th2, Th9, Th17 and regulatory T (T_reg) cells, which are essential for immune responses and cancer immunotherapy. However, the role of RNA N⁶-methyladenosine (m⁶A) modification in this differentiation is unclear. Here we show that YTHDF2, an important m⁶A reader protein known to destabilize m⁶A-modified mRNA, negatively regulates Th9 cell differentiation. Ablation of Ythdf2 in both mouse and human naive CD4⁺ T cells promotes Th9 differentiation by stabilizing Gata3 and Smad3 mRNA under interleukin-4 (IL-4) and transforming growth factor β (TGF-β) signaling, respectively. Ythdf2-deficient Th9 cells produce increased amounts of IL-9 and IL-2

SUBMITTER: Xiao S 

PROVIDER: S-EPMC12614224 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature