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

doi:10.1038/ni.3773

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

Journal article

Open access

Peer reviewed

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, …

Nature immunology, Vol.18(8), pp.931-939

08/2017

DOI: 10.1038/ni.3773

PMCID: PMC5564218

PMID: 28604718

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Abstract

Activated CD8 T cells differentiate into cytotoxic effector (T ) cells that eliminate target cells. How T 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 cells. Runx3-deficient CD8 T cells aberrantly upregulated genes characteristic of follicular helper T (T ) 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 program. Ablating Tcf7 in Runx3-deficient CD8 T cells prevented the upregulation of T 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 -lineage deviation.

Immunohistochemistry

Up-Regulation

Enzyme-Linked Immunosorbent Assay

Hepatocyte Nuclear Factor 1-alpha - genetics

Receptors, CXCR5 - genetics

Epigenesis, Genetic

Gene Expression Regulation

Lymphopoiesis - genetics

Reverse Transcriptase Polymerase Chain Reaction

Proto-Oncogene Proteins c-bcl-6 - genetics

Cell Lineage

Animals

Sequence Analysis, RNA

T-Lymphocytes, Helper-Inducer - cytology

Core Binding Factor Alpha 3 Subunit - genetics

Mice

T-Lymphocytes, Cytotoxic - cytology

Details

Title: Subtitle: The transcription factor Runx3 guards cytotoxic CD8 + effector T cells against deviation towards follicular helper T cell lineage
Creators: Qiang Shan - Department of Microbiology, University of Iowa, Iowa City, Iowa, USA
Zhouhao Zeng - Department of Physics, The George Washington University, Washington DC, USA
Shaojun Xing - Department of Microbiology, University of Iowa, Iowa City, Iowa, USA
Fengyin Li - Department of Microbiology, University of Iowa, Iowa City, Iowa, USA
Stacey M Hartwig - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Jodi A Gullicksrud - Interdisciplinary Immunology Graduate Program, University of Iowa, Iowa City, Iowa, USA
Samarchith P Kurup - Department of Microbiology, University of Iowa, Iowa City, Iowa, USA
Natalija Van Braeckel-Budimir - Department of Microbiology, University of Iowa, Iowa City, Iowa, USA
Yao Su - State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Science, Beijing, P.R. China
Matthew D Martin - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Steven M Varga - Interdisciplinary Immunology Graduate Program, University of Iowa, Iowa City, Iowa, USA
Ichiro Taniuchi - RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
John T Harty - Interdisciplinary Immunology Graduate Program, University of Iowa, Iowa City, Iowa, USA
Weiqun Peng - Department of Physics, The George Washington University, Washington DC, USA
Vladimir P Badovinac - Interdisciplinary Immunology Graduate Program, University of Iowa, Iowa City, Iowa, USA
Hai-Hui Xue - Interdisciplinary Immunology Graduate Program, University of Iowa, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Nature immunology, Vol.18(8), pp.931-939
DOI: 10.1038/ni.3773
PMID: 28604718
PMCID: PMC5564218
NLM abbreviation: Nat Immunol
ISSN: 1529-2908
eISSN: 1529-2916
Publisher: United States
Grant note: R01 AI114543 / NIAID NIH HHS R01 AI112579 / NIAID NIH HHS T32 AI007260 / NIAID NIH HHS S10 OD016199 / NIH HHS R01 GM113961 / NIGMS NIH HHS R01 AI042767 / NIAID NIH HHS R21 AI042767 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS R21 AI113806 / NIAID NIH HHS R01 AI121080 / NIAID NIH HHS I01 BX002903 / BLRD VA R21 AI119160 / NIAID NIH HHS R37 AI042767 / NIAID NIH HHS R21 AI115149 / NIAID NIH HHS
Language: English
Date published: 08/2017
Academic Unit: Graduate College Admin and Gen; Microbiology and Immunology; Pathology
Record Identifier: 9984047774502771

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