The transcription factor Runx3 guards cytotoxic CD8 + effector T cells against deviation towards follicular helper T cell lineage

Qiang Shan, Zhouhao Zeng, Shaojun Xing, Fengyin Li, Stacey M. Hartwig, Jodi A. Gullicksrud, Samarchith P. Kurup, Natalija Van Braeckel-Budimir, Yao Su, Matthew D. Martin, Steven M. Varga, Ichiro Taniuchi, John T. Harty, Weiqun Peng, Vladimir P. Badovinac, Hai Hui Xue

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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 languageEnglish (US)
Pages (from-to)931-939
Number of pages9
JournalNature immunology
Volume18
Issue number8
DOIs
StatePublished - Jul 19 2017
Externally publishedYes

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