論文 - 詳細
| RRC ID | 87525 |
|---|---|
| 著者 | Perkins B, Novis CL, Baessler A, Sircy LM, Thomas MM, Harrison-Chau M, Richens AW, Fuchs B, Nguyen NX, Flint K, Winter BS, Varley KE, Hale JS. |
| タイトル | Dnmt3a-dependent de novo DNA methylation enforces lineage commitment and preserves functionality of memory Th1 and Tfh cells. |
| ジャーナル | Cell Rep |
| Abstract |
Following acute viral infection, naive CD4+ T cells differentiate into T follicular helper (Tfh) and T helper 1 (Th1) cells that generate long-lived memory. However, it is unclear how memory Tfh and Th1 cells maintain their lineage commitment. We demonstrate that Tfh and Th1 lineages acquire distinct Dnmt3a-dependent de novo DNA methylation programs that are preserved into memory. Dnmt3a deletion impairs memory Th1 and Tfh cell lineage commitment and functionality, resulting in aberrant Runx1 upregulation that represses germinal center Tfh cell differentiation. In contrast, transient pharmacological DNA methyltransferase inhibition during priming impairs repression of Tfh-associated genes while properly silencing Runx1, resulting in enhanced primary and secondary germinal center Tfh cell responses. Together, these findings demonstrate that Dnmt3a-mediated DNA methylation programming is required to enforce T helper lineage commitment and preserve lineage-specific functions during the recall response to infection and reveal strategies to improve long-lived adaptive immunity against infectious diseases. |
| 巻・号 | 45(3) |
| ページ | 117062 |
| 公開日 | 2026-3-24 |
| DOI | 10.1016/j.celrep.2026.117062 |
| PII | S2211-1247(26)00140-3 |
| PMID | 41818240 |
| MeSH | Animals Cell Differentiation Cell Lineage* Core Binding Factor Alpha 2 Subunit / genetics Core Binding Factor Alpha 2 Subunit / metabolism DNA (Cytosine-5-)-Methyltransferases* / genetics DNA (Cytosine-5-)-Methyltransferases* / metabolism DNA Methylation* DNA Methyltransferase 3A Germinal Center / immunology Immunologic Memory* Mice Mice, Inbred C57BL T Follicular Helper Cells* / cytology T Follicular Helper Cells* / immunology T Follicular Helper Cells* / metabolism Th1 Cells* / cytology Th1 Cells* / immunology Th1 Cells* / metabolism |
| IF | 8.109 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 13 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 4.1 |
| リソース情報 | |
| 実験動物マウス | RBRC03731 |