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.
Pubmed ID: 29958803 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets CD90.2
View all literature mentionsThis unknown targets GOAT IGG FRACTION TO HAMSTER IGG (WHOLE MOLECULE)
View all literature mentionsThis monoclonal targets IL-17A
View all literature mentionsThis monoclonal targets CD90/CD90.1
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Human IL-2
View all literature mentionsThis monoclonal targets Rhesus IFN-g
View all literature mentionsThis monoclonal targets T-bet
View all literature mentionsThis monoclonal targets Ki-67
View all literature mentionsThis monoclonal targets CD62L
View all literature mentionsThis monoclonal targets CD44
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets I-Ab
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis monoclonal targets TCR Vbeta11
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets GM-CSF
View all literature mentionsThis monoclonal targets GM-CSF
View all literature mentionsThis monoclonal targets IFN-gamma
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD16/32
View all literature mentionsThis monoclonal targets IFNγ
View all literature mentionsThis monoclonal targets IL-4
View all literature mentionsThis monoclonal targets CD28
View all literature mentionsThis monoclonal targets CD3ε
View all literature mentionsThis monoclonal targets Ferritin mitochondrial antibody [EPR3004Y]
View all literature mentionsThis monoclonal targets ELAVL1, ELAVL2, ELAVL3, ELAVL4
View all literature mentionsThis polyclonal targets unknown
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsSoftware tools for Motif Discovery and next-gen sequencing analysis. Used for analyzing ChIP-Seq, GRO-Seq, RNA-Seq, DNase-Seq, Hi-C and numerous other types of functional genomics sequencing data sets. Collection of command line programs for unix style operating systems written in Perl and C++.
View all literature mentionsSoftware tool that removes adapter sequences from DNA sequencing reads.
View all literature mentionsBioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsMus musculus with name 129S(Cg)-Tfrctm3.1Nca/J from IMSR.
View all literature mentionsMus musculus with name B6.PL-Thy1a/CyJ from IMSR.
View all literature mentionsMus musculus with name B6.129S7-Rag1tm1Mom/J from IMSR.
View all literature mentionsMus musculus with name B6.Cg-Tg(Cd4-cre)1Cwi/BfluJ from IMSR.
View all literature mentionsMus musculus with name C57BL/6-Tg(Tcra2D2.Tcrb2D2)1Kuch/J from IMSR.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsCell line Jurkat E6.1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis unknown targets GOAT IGG FRACTION TO HAMSTER IGG (WHOLE MOLECULE)
View all literature mentionsThis monoclonal targets CD90.2
View all literature mentions