| RRC ID |
83176
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| 著者 |
O'Hara J, Dakle P, Nguyen MLT, Barugahare A, Bennett TJ, Udupa VA, Murray N, Schlegel G, Kapouleas C, Li J, Turner SJ, Russ BE.
|
| タイトル |
Notch dependent chromatin remodeling enables Gata3 binding and drives lineage specific CD8+ T cell function.
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| ジャーナル |
Immunol Cell Biol
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| Abstract |
Activation of CD8+ T cells enable them to control virus infections and tumors. This process involves the differentiation of naïve CD8+ T cells into effector and memory states, driven by specific transcription factors (TFs). Previously, we have shown that Granzyme A (Gzma) induction in activated CD8+ T cells depends on Gata3 and the establishment of a permissive chromatin landscape at the Gzma locus. Interestingly, Gzma expression is independent of IL-4 signaling, which typically upregulates Gata3 in CD4+ T cells, suggesting an alternative pathway for Gata3 induction. Here we demonstrate that Notch signals during CD8+ T cell activation promote Gzma expression. Inhibition of Notch signaling or loss of the Notch transactivator Rbp-j leads to reduced Gzma expression, with transcriptionally repressive chromatin at the Gzma locus. The genome targets of Gata3 differ in effector CD8+ T cells activated with IL-4 compared with those activated with Notch signals or isolated after IAV infection. This indicates that the signals received during CD8+ T cell activation can alter the chromatin landscape, affecting Gata3 function. Furthermore, Gata3 deficiency results in reduced IAV-specific CD8+ T cell responses and decreased Gzma expression, although the Gzma locus maintains a permissive chromatin landscape. These findings suggest that Notch signals received by virus-specific CD8+ T cells prepare the chromatin landscape for Gata3 binding to CD8+ lineage-specific gene loci, promoting effective CD8+ T cell immunity.
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| 公開日 |
2025-2-26
|
| DOI |
10.1111/imcb.70002
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| PMID |
40012375
|
| IF |
3.764
|
| リソース情報 |
| 実験動物マウス |
RBRC01071 |
