Cell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathways

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dc.citation.articleNumber493
dc.citation.journalTitleNature Communications
dc.citation.volumeNumber9
dc.contributor.authorCzerkies, Maciej
dc.contributor.authorKorwek, Zbigniew
dc.contributor.authorPrus, Wiktor
dc.contributor.authorKochańczyk, Marek
dc.contributor.authorJaruszewicz-Błońska, Joanna
dc.contributor.authorTudelska, Karolina
dc.contributor.authorBłoński, Sławomir
dc.contributor.authorKimmel, Marek
dc.contributor.authorBrasier, Allan R.
dc.contributor.authorLipniacki, Tomasz
dc.date.accessioned2018-07-11T18:51:12Z
dc.date.available2018-07-11T18:51:12Z
dc.date.issued2018
dc.description.abstractThe innate immune system processes pathogen-induced signals into cell fate decisions. How information is turned to decision remains unknown. By combining stochastic mathematical modelling and experimentation, we demonstrate that feedback interactions between the IRF3, NF-κB and STAT pathways lead to switch-like responses to a viral analogue, poly(I:C), in contrast to pulse-like responses to bacterial LPS. Poly(I:C) activates both IRF3 and NF-κB, a requirement for induction of IFNβ expression. Autocrine IFNβ initiates a JAK/STAT-mediated positive-feedback stabilising nuclear IRF3 and NF-κB in first responder cells. Paracrine IFNβ, in turn, sensitises second responder cells through a JAK/STAT-mediated positive feedforward pathway that upregulates the positive-feedback components: RIG-I, PKR and OAS1A. In these sensitised cells, the ‘live-or-die’ decision phase following poly(I:C) exposure is shorter—they rapidly produce antiviral responses and commit to apoptosis. The interlinked positive feedback and feedforward signalling is key for coordinating cell fate decisions in cellular populations restricting pathogen spread.
dc.identifier.citationCzerkies, Maciej, Korwek, Zbigniew, Prus, Wiktor, et al.. "Cell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathways." <i>Nature Communications,</i> 9, (2018) Springer Nature: https://doi.org/10.1038/s41467-017-02640-8.
dc.identifier.doihttps://doi.org/10.1038/s41467-017-02640-8
dc.identifier.urihttps://hdl.handle.net/1911/102390
dc.language.isoeng
dc.publisherSpringer Nature
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. 
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleCell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathways
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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