GEO series

Themis directs T cell exhaustion by promoting PD-1 signaling and regulating expression of transcription factors TCF-1 and TOX

GSE285487 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2025/12/25 Platform GPL28457

Summary

T cell exhaustion is a protective mechanism during chronic viral infections, but it can impair anti-tumor immunity. Themis, a T cell-specific protein, is critical for CD8+ T cell homeostasis, cytokine responsiveness, and anti-Listeria responses. In Themis-deficient mice infected with LCMV C13, a chronic virus, we observed severe lung injury and premature death. Single-cell analysis revealed that Themis-deficient effector CD8+ T cells, while producing higher levels of TNF and IFN-γ, were impaired in population expansion due to poor cell sustainability. Biochemical studies showed that Themis binds PD-1, promoting PD-1 phosphorylation and SHP-2 recruitment. Beyond its role in restraining effector T cell function, Themis is essential for the development of Tpex cells by promoting TCF-1 expression and driving transcriptional and epigenetic changes. Moreover, Themis supports TOX and PD-1 expression, ensuring the maintenance of terminally exhausted T cells (Tex). This study reveals the multifaceted roles of Themis in the progression of T cell exhaustion.

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Also filed as BioProject PRJNA1204081 and SRA study SRP554289. Searching any of these in the dataset finder brings you back here.

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