Unknown

Dataset Information

0

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

ABSTRACT: Activated CD8+ T cells differentiate into cytotoxic effector (TEFF) cells that eliminate target cells. How TEFF 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 TEFF cells. Runx3-deficient CD8+ TEFF cells aberrantly upregulated genes characteristic of follicular helper T (TFH) cell lineage, including Bcl6, Tcf7 and Cxcr5. Mechanistically, the Runx3-CBF? transcription factor complex deployed H3K27me3 to Bcl6 and Tcf7 genes to suppress the TFH program. Ablating Tcf7 in Runx3-deficient CD8+ TEFF cells prevented the upregulation of TFH 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 TFH-lineage deviation.

SUBMITTER: Shan Q 

PROVIDER: S-EPMC5564218 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Activated CD8<sup>+</sup> T cells differentiate into cytotoxic effector (T<sub>EFF</sub>) cells that eliminate target cells. How T<sub>EFF</sub> 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<sub>EFF</sub> cells. Runx3-deficient CD8<sup>+</sup> T<sub>EFF</sub> cells aberrantly upregulated genes characteristic of follicular helper T (T<sub>FH</sub>) cell lineage, inc  ...[more]

Similar Datasets

Unknown CXCR5<sup>+</sup>PD-1<sup>+</sup> follicular helper CD8 T cells control B cell tolerance.
| S-EPMC6765049 | biostudies-literature
Unknown CD4<sup>+</sup>CD8<sup>+</sup> T follicular helper cells regulate humoral immunity in chronic inflammatory lesions.
| S-EPMC9452889 | biostudies-literature
Unknown SLAMF7 and IL-6R define distinct cytotoxic versus helper memory CD8<sup>+</sup> T cells.
| S-EPMC7733515 | biostudies-literature
Unknown Kinetics of CD4<sup>+</sup> T Helper and CD8<sup>+</sup> Effector T Cell Responses in Acute Dengue Patients.
| S-EPMC7542683 | biostudies-literature
Unknown Conversion of effector CD4<sup>+</sup> T cells to a CD8<sup>+</sup> MHC II-recognizing lineage.
| S-EPMC7853072 | biostudies-literature
Unknown Follicular helper-T cells restore CD8<sup>+</sup>-dependent antitumor immunity and anti-PD-L1/PD-1 efficacy.
| S-EPMC8190041 | biostudies-literature
Unknown Primary germinal center-resident T follicular helper cells are a physiologically distinct subset of CXCR5<sup>hi</sup>PD-1<sup>hi</sup> T follicular helper cells.
| S-EPMC8842852 | biostudies-literature
Unknown Intestinal CD8<sup>+</sup> T cell responses are abundantly induced early in human development but show impaired cytotoxic effector capacities.
| S-EPMC8075922 | biostudies-literature
Unknown Interconnected subsets of memory follicular helper T cells have different effector functions.
| S-EPMC5635037 | biostudies-literature
Unknown HDAC3 restrains CD8-lineage genes to maintain a bi-potential state in CD4<sup>+</sup>CD8<sup>+</sup> thymocytes for CD4-lineage commitment.
| S-EPMC6338460 | biostudies-literature