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Omics · study · 2026

Transcriptional Regulation by NFATc1 and NFATc2 in chronically activated CD8+ T cells

Listed in NCBI GEO

Both chronic viral infections and progressing tumors result in dysfunctional CD8+T cells in a process called exhaustion.

Description

Such TEX cells exhibit a reduced proliferative capacity, reduced cytokine expression and target cell killing. They are characterized by increased expression of co-inhibitory receptors as PD-1, Tim-3, Lag-3 and TIGIT, and resistance against immune checkpoint therapies (ICT).

These cells develop from so called precursors of exhaustion (TPEX) that express high levels of TCF1 and Ly108 and still respond to ICT. The NFAT factors NFATc1 and NFATc2 play a crucial role in exhaustion of CD8+ T cells and, thereby, in suppression of tumor formation by immune cells. NFATc1 is the most prominent NFAT factor in nuclei of activated T cells and the inducible isoform NFATc1/aA, is strongly expressed in chronically induced CD8+ T cells.

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The inducible expression of NFATc1/aA is controlled by the distal enhancer E2 and conditional ablation of E2 abolish this induction. We compared here the transcriptome of in vitro chronically stimulated CD8+ T cells with different NFAT deficiencies. While the ablation of NFATc2 resulted in reduced expression of exhaustion markers Tim3 and Tigit and increased expression of Tcf7 and Slamf6, only minor effects on exhaustion markers were detected upon ablation of inducible NFAT1/aA or entire NFATc1.

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From keywords
Life Sciences
Inferred from text
Cancer 65%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE25349213 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title