English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

CD8 expression in T lymphocytes is tightly regulated by the activity of at least six  Cd8  enhancers (E8 I -E8 VI ), however their complex developmental stage-, subset-, and lineage-specific interplays are incompletely understood. Here we analyzed ATAC-seq data on the Immunological Genome Project database and identified a similar developmental regulation of chromatin accessibility of a subregion of E8 I , designated E8 I -core, and of E8 VI . Loss of E8 I -core led to a similar reduction in CD8 expression in naïve CD8 +  T cells and in IELs as observed in  E8   I   −/−  mice, demonstrating that we identified the core enhancer region of E8 I . While  E8   VI   −/−  mice displayed a mild reduction in CD8 expression levels on CD8SP thymocytes and peripheral CD8 +  T cells, CD8 levels were further reduced upon combined deletion of E8 I -core and E8 VI . Moreover, activated  E8   I   - core −/−  E8   VI   −/−  CD8 +  T cells lost CD8 expression to a greater degree than  E8   I   - core −/−  and  E8   VI   −/−  CD8 +  T cells, suggesting that the combined activity of both enhancers is required for establishment and maintenance of CD8 expression before and after TCR activation. Finally, we observed a severe reduction of CD4 CTLs among the TCRβ + CD4 +  IEL population in  E8   I   - core −/−  but not  E8   VI   −/−  mice. Such a reduction was not observed in  Cd8a  −/−  mice, indicating that E8 I -core controls the generation of CD4 CTLs independently of its role in  Cd8a  gene regulation. Further, the combined deletion of E8 I -core and E8 VI  restored CD4 CTL subsets, suggesting an antagonistic function of E8 VI  in the generation of CD4 CTLs. Together, our study demonstrates a complex utilization and interplay of E8 I -core and E8 VI  in regulating CD8 expression in cytotoxic lineage T cells and in IELs. Moreover, we revealed a novel E8 I -mediated regulatory mechanism controlling the generation of intestinal CD4 CTLs.

Differential Requirement of Cd8 Enhancers E8I and E8VI in Cytotoxic Lineage T Cells and in Intestinal Intraepithelial Lymphocytes