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

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dc.citation.articleNumber493en_US
dc.citation.journalTitleNature Communicationsen_US
dc.citation.volumeNumber9en_US
dc.contributor.authorCzerkies, Maciejen_US
dc.contributor.authorKorwek, Zbigniewen_US
dc.contributor.authorPrus, Wiktoren_US
dc.contributor.authorKochańczyk, Mareken_US
dc.contributor.authorJaruszewicz-Błońska, Joannaen_US
dc.contributor.authorTudelska, Karolinaen_US
dc.contributor.authorBłoński, Sławomiren_US
dc.contributor.authorKimmel, Mareken_US
dc.contributor.authorBrasier, Allan R.en_US
dc.contributor.authorLipniacki, Tomaszen_US
dc.contributor.orgBioengineeringen_US
dc.contributor.orgStatisticsen_US
dc.date.accessioned2018-07-11T18:51:12Zen_US
dc.date.available2018-07-11T18:51:12Zen_US
dc.date.issued2018en_US
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.en_US
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.en_US
dc.identifier.doihttps://doi.org/10.1038/s41467-017-02640-8en_US
dc.identifier.urihttps://hdl.handle.net/1911/102390en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
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. en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleCell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathwaysen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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