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    Macrophage migration inhibitory factor is required for NLRP3 inflammasome activation

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    Author
    Lang, T; Lee, JPW; Elgass, K; Pinar, AA; Tate, MD; Aitken, EH; Fan, H; Creed, SJ; Deen, NS; Traore, DAK; ...
    Date
    2018-06-08
    Source Title
    Nature Communications
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Mueller, Ivo; Aitken, Elizabeth
    Affiliation
    Medical Biology (W.E.H.I.)
    Medicine and Radiology
    Metadata
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    Document Type
    Journal Article
    Citations
    Lang, T., Lee, J. P. W., Elgass, K., Pinar, A. A., Tate, M. D., Aitken, E. H., Fan, H., Creed, S. J., Deen, N. S., Traore, D. A. K., Mueller, I., Stanisic, D., Baiwog, F. S., Skene, C., Wilce, M. C. J., Mansell, A., Morand, E. F. & Harris, J. (2018). Macrophage migration inhibitory factor is required for NLRP3 inflammasome activation. NATURE COMMUNICATIONS, 9 (1), https://doi.org/10.1038/s41467-018-04581-2.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255207
    DOI
    10.1038/s41467-018-04581-2
    Abstract
    Macrophage migration inhibitory factor (MIF) exerts multiple effects on immune cells, as well as having functions outside the immune system. MIF can promote inflammation through the induction of other cytokines, including TNF, IL-6, and IL-1 family cytokines. Here, we show that inhibition of MIF regulates the release of IL-1α, IL-1β, and IL-18, not by affecting transcription or translation of these cytokines, but via activation of the NLRP3 inflammasome. MIF is required for the interaction between NLRP3 and the intermediate filament protein vimentin, which is critical for NLRP3 activation. Further, we demonstrate that MIF interacts with NLRP3, indicating a role for MIF in inflammasome activation independent of its role as a cytokine. These data advance our understanding of how MIF regulates inflammation and identify it as a factor critical for NLRP3 inflammasome activation.

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