Disease relevance of EOMES

• We now report that IL-12, a signature of cell-mediated immunity, represses Eomes while positively regulating T-bet in effector CD8(+) T cells during infection with Listeria monocytogenes [1].
• To this end, we have identified a human renal cell carcinoma line (UMRC6) that is representative of localized, nonmetastatic RCC, reflecting a loss of TBR3, but not TBR2 expression [2].

High impact information on EOMES

• Homozygous silencing of T-box transcription factor EOMES leads to microcephaly with polymicrogyria and corpus callosum agenesis [3].
• Together with the expression pattern of EOMES in the developing human brain, our data suggest that EOMES is involved in neuronal division and/or migration [3].
• We report an autosomal recessive microcephaly syndrome cosegregating with a homozygous balanced translocation between chromosomes 3p and 10q, and we show that a position effect at the breakpoint on chromosome 3 silences the eomesodermin transcript (EOMES), also known as T-box-brain2 (TBR2) [3].
• Recently, it has been reported that Eomesodermin (Eomes), a member of the T-box gene family, is expressed in developing CD8(+) T cells and plays an important role in regulating IFN-gamma production and cytolytic effector function [4].
• In this study, we show that Eomes mRNA and protein are also expressed in developing Th1 cells, and exposure of naive Thp cells to IL-21 results in a decrease in Eomes expression [4].

Biological context of EOMES

• We propose that loss of TBR3 is necessary for RCC carcinogenesis, and that loss of TBR2 leads to acquisition of a metastatic phenotype [2].
• Restoring TBR2 and TBR3 expression in UMRC3 cells attenuates cell proliferation, completely restores TGFbeta-mediated transcriptional responses, and completely blocks anchorage independent-growth: while restoration of TBR2 partially restores TGFbeta-mediated signaling [2].
• We also noted that the P. flava homolog of T-brain/Eomes, a gene closely related by sequence and expression around the blastopore to Brachyury and associated with development of the vertebrate brain, also exhibits early posterior expression around the blastopore and a field of de novo anterior ectoderm expression during later embryogenesis [5].
• Marker gene expression (Eomes, Pl-1, Tpbp) and invasion assays showed that TS cells exhibit increased invasive capacity when differentiating into giant cells and spongiotrophoblasts in unconditioned media without FGF-4 and heparin [6].
• Conserved synteny between regions of the human and zebrafish genomes, gene organization and phylogenetic analysis all indicate that the zebrafish Eomes2 gene is a homologue of mammalian Eomes, as previously found for zebrafish Eomes1 [7].

Anatomical context of EOMES

• Little is known, however, about how cytokines regulate expression of T-bet and eomesodermin (Eomes) in effector and memory CD8(+) T cells [1].
• Another cell line, UMRC3, is highly metastatic, having lost TBR3 and TBR2 expression [2].
• No information is available on the role of Eomes in the immune system of lower vertebrates to date, although developmental studies on Eomes (Eomes1) have been performed in zebrafish [7].
• However, strong expression of both Eomes mRNAs was detected in the leukocytes from the spleen, followed by those from body kidney and peripheral blood, with expression of Eomes1 always stronger than that of Eomes2 [7].
• Eomes is also expressed in CD8(+) T cells and NK cells [7].

References