Abstract
Activated CD8 + T cells differentiate into cytotoxic effector (T EFF) cells that eliminate target cells. How T EFF cell identity is established and maintained is not fully understood. We found that Runx3 deficiency limited clonal expansion and impaired upregulation of cytotoxic molecules in T EFF cells. Runx3-deficient CD8 + T EFF cells aberrantly upregulated genes characteristic of follicular helper T (T FH) cell lineage, including Bcl6, Tcf7 and Cxcr5. Mechanistically, the Runx3-CBFβ transcription factor complex deployed H3K27me3 to Bcl6 and Tcf7 genes to suppress the T FH program. Ablating Tcf7 in Runx3-deficient CD8 + T EFF cells prevented the upregulation of T FH genes and ameliorated their defective induction of cytotoxic genes. As such, Runx3-mediated Tcf7 repression coordinately enforced acquisition of cytotoxic functions and protected the cytotoxic lineage integrity by preventing T FH -lineage deviation.
Original language | English (US) |
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Pages (from-to) | 931-939 |
Number of pages | 9 |
Journal | Nature immunology |
Volume | 18 |
Issue number | 8 |
DOIs | |
State | Published - Jul 19 2017 |
Externally published | Yes |