Human Sox4 facilitates the development of CXCL13-producing helper T cells in inflammatory environments

Nature Communications
Hiroyuki YoshitomiJunya Toguchida

Abstract

In human inflammatory sites, PD-1hiCXCR5-CD4+ T cells are involved in the formation of ectopic lymphoid-like structures (ELSs) by the secretion of chemokine CXCL13, but how the transcription of CXCL13 is regulated in CD4+ T cells is still unclear. Here we show that Sox4 is a key transcription factor for CXCL13 production in human CD4+ T cells under inflammatory conditions. In vitro TGF-β+, IL-2-neutralizing culture conditions give rise to PD-1hiCXCR5-CD4+ T cells that preferentially express CXCL13, and transcriptome analysis and lentiviral overexpression indicate Sox4 association with the CXCL13 transcription. In vivo, Sox4 is significantly upregulated in synovial CD4+ T cells, when compared with blood CD4+ T cells, from patients with rheumatoid arthritis (RA), and further correlates with ELS formation in RA synovium. Overall, our studies suggest that Sox4 contributes to CXCL13 production and ELS formation at inflammatory sites in humans.

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Citations

Jan 23, 2020·International Immunology·Nagahiro MinatoYoko Hamazaki
Jun 26, 2020·Immunological Medicine·Hiroyuki Yoshitomi
Sep 2, 2020·Cellular & Molecular Immunology·Hiroyuki Yoshitomi, Hideki Ueno
Oct 30, 2020·Nucleic Acids Research·Nikolaos-Kosmas ChlisFabian J Theis
Feb 16, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anuja SatheHanlee P Ji
Dec 18, 2020·JCI Insight·Camille-Charlotte BalançaMaha Ayyoub
Apr 22, 2021·Cellular and Molecular Life Sciences : CMLS·Jian LuShengjun Wang
Jun 1, 2021·Immunological Medicine·Hisakata Yamada
Dec 17, 2021·Science·Liangtao ZhengZemin Zhang

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Datasets Mentioned

BETA
GSE15659

Methods Mentioned

BETA
PCR
flow cytometry
PMA
Fluorescence

Software Mentioned

JMP Pro
FlowJo

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