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

Abstract

In human inflammatory sites, PD-1^hiCXCR5^-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^hiCXCR5^-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.