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Human Sox4 facilitates the development of CXCL13-producing helper T cells in inflammatory environments
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Human Sox4 facilitates the development of CXCL13-producing helper T cells in inflammatory environments
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Journal Article
Human Sox4 facilitates the development of CXCL13-producing helper T cells in inflammatory environments
2018
Overview
In human inflammatory sites, PD-1
hi
CXCR5
−
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-1
hi
CXCR5
−
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.
At inflammatory sites, ectopic lymphoid-like structures (ELS) can be induced through the function of chemokine CXCL13 produced by CD4
+
T cells. Here the authors show that a transcription factor, Sox4, induces the expression of CXCL13 in CD4 T cells in vitro, and is associated with ELS formation in patients with rheumatoid arthritis.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 13/44
/ 13/51
/ 13/95
/ 14/35
/ 14/63
/ 38/61
/ 38/89
/ 42/70
/ 64/60
/ 96/21
/ 96/95
/ Adult
/ Aged
/ Arthritis, Rheumatoid - blood
/ Arthritis, Rheumatoid - immunology
/ Arthritis, Rheumatoid - pathology
/ Cell Differentiation - immunology
/ Chemokine CXCL13 - immunology
/ Chemokine CXCL13 - metabolism
/ Female
/ Humanities and Social Sciences
/ Humans
/ Male
/ Science
/ SOXC Transcription Factors - metabolism
/ Synovial Membrane - pathology
/ Synovium
/ T-Lymphocytes, Helper-Inducer - immunology
