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Cited by 122Psoriasis: Treatment and PathogenesisT-cell and B-cell ImmunologySystemic Lupus Erythematosus Research

IL-6/STAT3 pathway induced deficiency of RFX1 contributes to Th17-dependent autoimmune diseases via epigenetic regulation

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Zhao, Ming, Tan, Yixin, Peng, Qiao, Huang, Cancan, Guo, Yu, Liang, Gongping, Zhu, Bochen, Huang, Yi +8 more·2018·Nature Communications
DOI 10.1038/s41467-018-02890-0PMC PMC5805701
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Abstract

Epigenetic modifications affect the differentiation of T cell subsets and the pathogenesis of autoimmune diseases, but many mechanisms of epigenetic regulation of T cell differentiation are unclear. Here we show reduced expression of the transcription factor RFX1 in CD4+ T cells from patients with systemic lupus erythematosus, which leads to IL-17A overexpression through increased histone H3 acetylation and decreased DNA methylation and H3K9 tri-methylation. Conditional deletion of Rfx1 in mice exacerbates experimental autoimmune encephalomyelitis and pristane-induced lupus-like syndrome and increases induction of Th17 cells. In vitro, Rfx1 deficiency increases the differentiation of naive CD4+ T cells into Th17 cells, but this effect can be reversed by forced expression of Rfx1. Importantly, RFX1 functions downstream of STAT3 and phosphorylated STAT3 can inhibit RFX1 expression, highlighting a non-canonical pathway that regulates differentiation of Th17 cells. Collectively, our findings identify a unique role for RFX1 in Th17-related autoimmune diseases.

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  • The c.*935G>A variant is not located in a known miRNA binding site according to PicTar and miRDB.

    “However, this variant is not located in a known miRNA binding site according to PicTar and miRDB database [22,23].”

    From Identification of Genetic Variants Regulating the Abundance of Clinically Relevant Plasma Proteins using the Diversity Outbred Mouse Model (2021) · cites this paper as [23]

    The Results section on RFX1 regulation of the IL17A locus discusses predicted transcription-factor binding sites, not miRNA binding sites. Searches for c.*935G>A, PicTar, miRDB, and miRNA binding sites found no passage addressing the variant or the claimed database result. Page numbers were not available in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 45

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Authors
Zhao, M., Tan, Y., Peng, Q., Huang, C., Guo, Y., Liang, G., Zhu, B., Huang, Y., Liu, A., Wang, Z., Li, M., Gao, X., Wu, R., Wu, H., Long, H., & Lu, Q.
Affiliations
Second Xiangya Hospital of Central South University (CN)
Corresponding author
  • Zhao, Ming
  • Lu, Qianjin
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-02-08
Volume
9
Issue
1
Pages
583-583
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-018-02890-0
PMC
PMC5805701
OpenAlex
W2805319241
Cited by
122
References
0
Citations by year
2026: 6 · 2025: 11 · 2024: 10 · 2023: 12 · 2022: 18 · 2021: 26 · 2020: 16 · 2019: 15 · 2018: 8
FWCI
6.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (81270024, 81522038, 81220108017)
  • Central South University (2016CX029)
  • Natural Science Foundation of Hunan Province (14JJ1009)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
Keywords
RFX1, Th17 cells, IL-6/STAT3 signaling, epigenetic regulation, CD4+ T cell differentiation, systemic lupus erythematosus, experimental autoimmune encephalomyelitis, histone H3 acetylation, DNA methylation, H3K9 trimethylation, IL-17A, transcription factor regulation
MeSH terms
Regulatory Factor X1, Adolescent, Adult, Animals, Cell Differentiation, Cells, Cultured, Encephalomyelitis, Autoimmune, Experimental, Female, Humans, Lupus Erythematosus, Systemic, Male, Mice, Inbred C57BL, Middle Aged, Phosphorylation, Signal Transduction, CD4-Positive T-Lymphocytes, Interleukin-6, Mice, Knockout, Jurkat Cells, Epigenesis, Genetic, STAT3 Transcription Factor, Young Adult, HEK293 Cells, Th17 Cells

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