RRC ID 54228
Author Yoshitomi H, Kobayashi S, Miyagawa-Hayashino A, Okahata A, Doi K, Nishitani K, Murata K, Ito H, Tsuruyama T, Haga H, Matsuda S, Toguchida J.
Title Human Sox4 facilitates the development of CXCL13-producing helper T cells in inflammatory environments.
Journal Nat Commun
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.
Volume 9(1)
Pages 3762
Published 2018-9-19
DOI 10.1038/s41467-018-06187-0
PII 10.1038/s41467-018-06187-0
PMID 30232328
PMC PMC6145936
MeSH Adult Aged Arthritis, Rheumatoid / blood Arthritis, Rheumatoid / immunology* Arthritis, Rheumatoid / pathology Cell Differentiation / immunology Chemokine CXCL13 / genetics* Chemokine CXCL13 / immunology Chemokine CXCL13 / metabolism Female Gene Expression Profiling Healthy Volunteers Humans Male Middle Aged SOXC Transcription Factors / metabolism* Synovial Membrane / pathology T-Lymphocytes, Helper-Inducer / immunology* T-Lymphocytes, Helper-Inducer / metabolism Up-Regulation
IF 11.878
Times Cited 9
Resource
DNA material CSII-EF-MCS-IRES2-Venus (RDB04384) CS-RfA-EG (RDB04391) CSII-EF-IRES2-Venus_hMAF (RDB17306) CSII-EF-IRES2-Venus_hTOX (RDB17307) CSIIR-EF-MCS-IRES2-Venus (RDB17308) CSII-EF-IRES2-Venus_hPRDM1a (RDB17309) CSII-EF-IRES2-Venus_mSOX4 (RDB17310) CSII-EF-IRES2-Venus_hSOX4 (RDB17311) CSII-EF-IRES2-Venus_hSOX4 deltaN56 (RDB17312) CSII-EF-IRES2-Venus_hSOX4 deltaHMG (RDB17313) CSII-EF-IRES2-Venus_hSOX4 deltaGRR (RDB17314) CSII-EF-IRES2-Venus_hSOX4 deltaSRR (RDB17315) CSII-EF-IRES2-Venus_hSOX4 deltaC33 (RDB17316) CSII-EF-IRES2-Venus_hSOX4 deltaC52 (RDB17317) CSU6EG_sh-CTL (RDB17318) CSU6EG_sh7D-hSOX4 (RDB17319)