Research ArticleInnate Immunity

The interaction between IKKα and LC3 promotes type I interferon production through the TLR9-containing LAPosome

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Science Signaling  01 May 2018:
Vol. 11, Issue 528, eaan4144
DOI: 10.1126/scisignal.aan4144

LC3 recruits IKKα after TLR9 activation

Toll-like receptor 9 (TLR9) is a pattern recognition receptor involved in innate sensing of extracellular DNA within the endosomes of phagocytes. Hayashi et al. found that IKKα kinase associated with the autophagy protein LC3 deposited on endosomes after TLR9 stimulation of macrophages. Formation of this LC3-IKKα signaling platform through noncanonical autophagy also recruited other effectors involved in type I interferon signaling. Mutagenesis of LC3-interacting regions in IKKα suggested that these effects were mediated by a direct interaction of the kinase with LC3. Together, these data identify IKKα as a critical component of LC3-associated phagocytosis-mediated endosome-based signaling platforms necessary for stimulating type I interferon production after TLR9 engagement.

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