Macrophage migration inhibitory factor is required for NLRP3 inflammasome activation

Lang T, Lee JPW, Deen NS, Morand EF and Harris J

Centre for Inflammatory Diseases, Monash University.

Macrophage migration inhibitory factor (MIF) exerts multiple effects on immune cells, as well as having functions outside of the immune system. However, despite over 50 decades of research, the mechanisms by which it does so are not well understood. MIF can promote inflammation through the induction of other cytokines, including TNF, IL-6 and IL-1 family cytokines. We have found that inhibition of MIF regulates the release of IL-1α, IL-1β and IL-18 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.