Pré-Publication, Document De Travail Année : 2024

Post-transcriptional regulation by TIA1 and TIAL1 controls the transcriptional program enforcing T cell quiescence

Résumé

Immune protection against new and recurrent infections relies on long-term maintenance of a highly diversified T-cell repertoire. Transcription factors cooperate to enforce T-cell metabolic quiescence and maintenance. However, less is known about the post-transcriptional networks that preserve peripheral naïve T cells. Here we describe the RNA binding proteins TIA1 and TIAL1 as key promoters of CD4 and CD8 T cell quiescence. T cells deficient in TIA1 and TIAL1 undergo uncontrolled cell proliferation in the absence of cognate antigens, leading this to a premature T-cell activation, exhaustion and death. Mechanistically, TIA1 and TIAL1 control the expression of master regulatory transcription factors, FOXP1, LEF1 and TCF1, that restrain homeostatic T-cell proliferation. In summary, our study highlights a previously unrecognised dependency on post-transcriptional gene regulation by TIA1 and TIAL1 for implementing the quiescent transcriptional programs for long survival of T cells.
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Dates et versions

hal-04888124 , version 1 (15-01-2025)

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Ines Osma-Garcia, Orlane Maloudi, Mailys Mouysset, Dunja Capitan-Sobrino, Trang-My Nguyen, et al.. Post-transcriptional regulation by TIA1 and TIAL1 controls the transcriptional program enforcing T cell quiescence. 2025. ⟨hal-04888124⟩
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