Cited by 156Iron Metabolism and DisordersT-cell and B-cell ImmunologyRNA Research and Splicing

Iron drives T helper cell pathogenicity by promoting RNA-binding protein PCBP1-mediated proinflammatory cytokine production

Open access
Wang, Zhizhang, Yin, Weijie, Zhu, Lizhen, Li, Jia, Yao, Yikun, Chen, Feifei, Sun, Mengmeng, Zhang, Jiayuan +3 more·2018·Immunity

Abstract

Iron deposition is frequently observed in human autoinflammatory diseases, but its functional significance is largely unknown. Here we showed that iron promoted proinflammatory cytokine expression in T cells, including GM-CSF and IL-2, via regulating the stability of an RNA-binding protein PCBP1. Iron depletion or Pcbp1 deficiency in T cells inhibited GM-CSF production by attenuating Csf2 3' untranslated region (UTR) activity and messenger RNA stability. Pcbp1 deficiency or iron uptake blockade in autoreactive T cells abolished their capacity to induce experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. Mechanistically, intracellular iron protected PCBP1 protein from caspase-mediated proteolysis, and PCBP1 promoted messenger RNA stability of Csf2 and Il2 by recognizing UC-rich elements in the 3' UTRs. Our study suggests that iron accumulation can precipitate autoimmune diseases by promoting proinflammatory cytokine production. RNA-binding protein-mediated iron sensing may represent a simple yet effective means to adjust the inflammatory response to tissue homeostatic alterations.

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Crossref · 10.1016/j.immuni.2018.05.008

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  • Iron protects PCBP1, an RNA binding protein which stabilizes GMCSF mRNA, from caspase-mediated proteolysis, leading to enhanced GMCSF production when iron levels are high within the T cell to drive inflammation.

    “It was demonstrated that iron protects PCBP1 (Poly(RC)-binding protein 1), an RNA binding protein which stabilizes GMCSF mRNA, from caspase-mediated proteolysis thus leading to enhanced GMCSF production when iron levels are high within the T cell to drive inflammation (Wang et al., 2018).”

    From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Wang et al., 2018

  • Iron directly participates in inflammatory responses by promoting proinflammatory cytokine production in T helper cells via poly(rC)-binding protein 1.

    “In a recent investigation it could be demonstrated that iron was able to directly participate in inflammatory responses by promoting proinflammatory cytokine production in T helper cells via poly(rC)-binding protein 1 [133].”

    From Iron in immune cell function and host defense (2021) · cites this paper as [133]

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Authors
Wang, Z., Yin, W., Zhu, L., Li, J., Yao, Y., Chen, F., Sun, M., Zhang, J., Shen, N., Song, Y., & Chang, X.
Affiliations
  • Shanghai Jiao Tong University (CN)
  • University of California San Diego (US)
Corresponding author
Chang, Xing
Venue
Immunity
Publisher
Elsevier BV
Published
2018-07
Volume
49
Issue
1
Pages
80-92.e7
ISSN
1074-7613 (ISSN-L)
OpenAlex
W2810518168
Cited by
156
References
66
Citations by year
2026: 14 · 2025: 15 · 2024: 28 · 2023: 26 · 2022: 31 · 2021: 20 · 2020: 13 · 2019: 8 · 2018: 1
FWCI
7.53
Type
journal article
Language
en
Open access
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • MOST (31370858, 81671552)
  • NSFC (13PJ1409300)
  • SMSTC
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
iron accumulation, T helper cells, PCBP1, RNA-binding proteins, inflammatory cytokines, GM-CSF, interleukin-2, mRNA stability, 3' untranslated region, experimental autoimmune encephalomyelitis, multiple sclerosis, autoinflammatory disease, iron sensing, autoreactive T cells
MeSH terms
Iron Deficiencies, Animals, Binding Sites, Carrier Proteins, Cell Line, DNA-Binding Proteins, Encephalomyelitis, Autoimmune, Experimental, Female, T-Lymphocytes, Helper-Inducer, Humans, Iron, Multiple Sclerosis, Receptors, Transferrin, RNA Processing, Post-Transcriptional, RNA, Messenger, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Cytokines, RNA-Binding Proteins, 3' Untranslated Regions, RNA Stability, RNA, Small Interfering, Mice

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