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Eomes regulates mitochondrial function and promotes survival of pathogenic CD4+ T cells during chronic inflammation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE247863 | GEO | 2023/12/23

REPOSITORIES: GEO

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Eomes regulates mitochondrial function and promotes survival of pathogenic CD4+ T cells during chronic inflammation [RNA-seq]

Project description:The tissue accumulation of T cells expressing the transcription factor Eomesodermin (Eomes) has been reported in several chronic inflammatory diseases, including multiple sclerosis. However, the mechanisms whereby Eomes controls this accumulation and strengthens inflammation remains ill-defined. Here, we show that Eomes deletion in antigen-specific CD4+ T cells is sufficient to protect against central nervous system (CNS) inflammation. We demonstrate that Eomes is dispensable for the initial priming of CD4+ T cells but is required for long-term maintenance of CNS-infiltrating CD4+ T cells. Our transcriptomic studies reveal that the impact Eomes on effector CD4+ T cell longevity is associated with sustained expression of multiple genes involved in mitochondrial organization and function. Accordingly, epigenetic studies demonstrate that Eomes supports mitochondrial function by direct binding to either metabolism-associated genes or mitochondrial transcriptional modulators. Besides, the significance of these findings was confirmed in both healthy donors and multiple sclerosis patients. CD4+ T cells expressing Eomes exhibit enhanced mitochondrial functions, which resulted in their increased capacity to survive upon prolonged in vitro stimulation. Together, our data reveal a new mechanism by which Eomes promotes severity and chronicity of inflammation via the enhancement of CD4+ T cell mitochondrial functions and resistance to stress-induced cell death.

2023-12-23 | GSE247862 | GEO

Eomes regulates mitochondrial function and promotes survival of pathogenic CD4+ T cells during chronic inflammation [ATAC-seq]

2023-12-23 | GSE247860 | GEO

Eomes regulates mitochondrial function and promotes survival of pathogenic CD4+ T cells during chronic inflammation [CUT&RUN]

2023-12-23 | GSE247861 | GEO