Foxk1 regulates effector T cell differentiation and function by repressing autophagy programs via the Akt-mTOR signaling pathway [Foxk1_RNA-seq]

ABSTRACT: Upon T Cell Receptor (TCR) engagement, the Akt-mTOR signaling cascade initiates downstream events that orchestrate metabolic reprogramming in T cells through the coordinated activation of distinct transcription factors (TFs). Here, we demonstrate that Foxk1 is an integrating component of the Akt-mTOR signaling program, mediating T cell activation and differentiation. Foxk1 deficiency leads to impaired effector functions in both CD4⁺ and CD8⁺ T cells, associated with defects in metabolic reprogramming. We demonstrate that this is due to Foxk1’s ability to repress autophagy-related genes within hours following TCR stimulation. Conversely, overexpression or enforced nuclear localization of Foxk1 enhances effector-like phenotype of T cells, leading to better anti-tumor responses. Our results demonstrate the central role played by Foxk1 in initiating T cell activation and in shaping their differentiation trajectory.

ORGANISM(S): Mus musculus

PROVIDER: GSE298556 | GEO | 2026/09/01

REPOSITORIES: GEO