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

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Iron Drives T Helper Cell Pathogenicity by Promoting RNA-Binding Protein PCBP1-Mediated Proinflammatory Cytokine Production

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Wang, Zhizhang, Yin, Weijie, Zhu, Lizhen, Li, Jia, Yao, Yikun, Chen, Feifei, Sun, Mengmeng, Zhang, Jiayuan, Shen, Nan, Song, Yan, Chang, Xing·2018·Immunity

DOI 10.1016/j.immuni.2018.05.008

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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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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
ORCID: Wang, Zhizhang
Yin, Weijie
Zhu, Lizhen
Li, Jia
Yao, Yikun
Sun, Mengmeng
Zhang, Jiayuan
Shen, Nan
Song, Yan
Chang, Xing
Venue: Immunity
Publisher: Elsevier BV
Published: 2018-07
Volume: 49
Issue: 1
Pages: 80-92.e7
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2018.05.008
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: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 382 d)
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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Iron Drives T Helper Cell Pathogenicity by Promoting RNA-Binding Protein PCBP1-Mediated Proinflammatory Cytokine Production

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