Transient T-bet Expression Functionally Specifies a Distinct T Follicular Helper Subset

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2018 Sep 21

PMID 30232200

Citations 53

Authors

Difeng Fang

Kairong Cui

Kairui Mao

Gangqing Hu

Rao Li

Mingzhu Zheng

Nicolas Riteau

Steven L Reiner

Alan Sher

Keji Zhao

Jinfang Zhu

Affiliations

Soon will be listed here.

Abstract

T follicular helper (Tfh) cells express transcription factor BCL-6 and cytokine IL-21. Mature Tfh cells are also capable of producing IFN-γ without expressing the Th1 transcription factor T-bet. Whether this IFN-γ-producing Tfh population represents a unique Tfh subset with a distinct differentiation pathway is poorly understood. By using T-bet fate-mapping mouse strains, we discovered that almost all the IFN-γ-producing Tfh cells have previously expressed T-bet and express high levels of NKG2D. DNase I hypersensitivity analysis indicated that the gene locus is partially accessible in this "ex-T-bet" population with a history of T-bet expression. Furthermore, multicolor tissue imaging revealed that the ex-T-bet Tfh cells found in germinal centers express IFN-γ in situ. Finally, we found that IFN-γ-expressing Tfh cells are absent in T-bet-deficient mice, but fully present in mice with T-bet deletion at late stages of T cell differentiation. Together, our findings demonstrate that transient expression of T-bet epigenetically imprints the locus for cytokine production in this Th1-like Tfh cell subset.

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