Macrophage migration inhibitory factor is required for NLRP3 inflammasome activation

Tali Lang, Jacinta P.W. Lee, Kirstin Elgass, Anita A. Pinar, Michelle D. Tate, Elizabeth H. Aitken, Huapeng Fan, Sarah J. Creed, Nadia S. Deen, Daouda A.K. Traore, Ivo Mueller, Danielle Stanisic, Francesca S. Baiwog, Colin Skene, Matthew C.J. Wilce, Ashley Mansell, Eric F. Morand, James Harris

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article number2223
Number of pages15
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Cite this

@article{2fd0ba78b27e4647a123d9a69eeae847,
title = "Macrophage migration inhibitory factor is required for NLRP3 inflammasome activation",
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.",
author = "Tali Lang and Lee, {Jacinta P.W.} and Kirstin Elgass and Pinar, {Anita A.} and Tate, {Michelle D.} and Aitken, {Elizabeth H.} and Huapeng Fan and Creed, {Sarah J.} and Deen, {Nadia S.} and Traore, {Daouda A.K.} and Ivo Mueller and Danielle Stanisic and Baiwog, {Francesca S.} and Colin Skene and Wilce, {Matthew C.J.} and Ashley Mansell and Morand, {Eric F.} and James Harris",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41467-018-04581-2",
language = "English",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

Macrophage migration inhibitory factor is required for NLRP3 inflammasome activation. / Lang, Tali; Lee, Jacinta P.W.; Elgass, Kirstin; Pinar, Anita A.; Tate, Michelle D.; Aitken, Elizabeth H.; Fan, Huapeng; Creed, Sarah J.; Deen, Nadia S.; Traore, Daouda A.K.; Mueller, Ivo; Stanisic, Danielle; Baiwog, Francesca S.; Skene, Colin; Wilce, Matthew C.J.; Mansell, Ashley; Morand, Eric F.; Harris, James.

In: Nature Communications, Vol. 9, No. 1, 2223, 01.12.2018.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Lang, Tali

AU - Lee, Jacinta P.W.

AU - Elgass, Kirstin

AU - Pinar, Anita A.

AU - Tate, Michelle D.

AU - Aitken, Elizabeth H.

AU - Fan, Huapeng

AU - Creed, Sarah J.

AU - Deen, Nadia S.

AU - Traore, Daouda A.K.

AU - Mueller, Ivo

AU - Stanisic, Danielle

AU - Baiwog, Francesca S.

AU - Skene, Colin

AU - Wilce, Matthew C.J.

AU - Mansell, Ashley

AU - Morand, Eric F.

AU - Harris, James

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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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