The Transcription Factor KLF2 Restrains CD4⁺ T Follicular Helper Cell Differentiation

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2015 Feb 19

PMID 25692701

Citations 110

Authors

June-Yong Lee

Cara N Skon

You Jeong Lee

Soohwan Oh

Justin J Taylor

Deepali Malhotra

Marc K Jenkins

M Geoffrey Rosenfeld

Kristin A Hogquist

Stephen C Jameson

Affiliations

Soon will be listed here.

Abstract

T follicular helper (Tfh) cells are essential for efficient B cell responses, yet the factors that regulate differentiation of this CD4(+) T cell subset are incompletely understood. Here we found that the KLF2 transcription factor serves to restrain Tfh cell generation. Induced KLF2 deficiency in activated CD4(+) T cells led to increased Tfh cell generation and B cell priming, whereas KLF2 overexpression prevented Tfh cell production. KLF2 promotes expression of the trafficking receptor S1PR1, and S1PR1 downregulation is essential for efficient Tfh cell production. However, KLF2 also induced expression of the transcription factor Blimp-1, which repressed transcription factor Bcl-6 and thereby impaired Tfh cell differentiation. Furthermore, KLF2 induced expression of the transcription factors T-bet and GATA3 and enhanced Th1 differentiation. Hence, our data indicate KLF2 is pivotal for coordinating CD4(+) T cell differentiation through two distinct and complementary mechanisms: via control of T cell localization and by regulation of lineage-defining transcription factors.

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