Pim1 promotes IFN-β production by interacting with IRF3

Ryeojin Ko, Jeongin Seo, Hana Park, Nawon Lee, Soo Young Lee

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The Pim (proviral integration site for Moloney murine leukemia virus) proteins compose a serine threonine kinase family whose members regulate cell proliferation, migration and cell survival. However, whether Pim kinases participate in innate immune responses is unclear. Here, we show for the first time that Pim1 plays an essential role in the production of interferon (IFN)-β by macrophages after their Toll-like receptor (TLR) pathway is activated by pathogen-associated molecular patterns (PAMPs). Specifically, Pim1 was quickly upregulated in an NF-κB-dependent manner after TLR stimulation with PAMPs. Pim1 deficiency reduced TLR3- or TLR4-stimulated IFN-β and IFN-stimulated gene (ISG) expression but not proinflammatory cytokine expression in macrophages. Mechanistically, Pim1 specifically upregulates IRF3 phosphorylation and nuclear translocation. However, this role is not dependent on Pim1 kinase activity. Rather, Pim1 appears to promote IRF3 phosphorylation by enhancing the formation of IFN-β signaling complexes composed of TRIF, TRAF3, TBK1, and IRF3. Poly (I:C)-treated Pim1−/− mice produced less serum IFN-β and were less likely to survive than wild-type mice. These findings show for the first time that Pim1 participates in TLR-mediated IFN-β production, thus revealing a novel target for controlling antiviral innate immune responses.

Original languageEnglish
Pages (from-to)2092-2103
Number of pages12
JournalExperimental and Molecular Medicine
Volume54
Issue number11
DOIs
StatePublished - Nov 2022

Bibliographical note

Funding Information:
We thank N.S. Kim (Chonnam University), W.S. Ryu (Yonsei University), and J.Y. Lee (Catholic University) for sharing cell lines and plasmids. This work was supported by grants from the National Research Foundation of Korea (2021R1A2C3003675 and 2019R1A5A6099645 to S.Y.L.; 2020R1I1A1A01054670 to R.K.) and by a Korea Basic Science Institute National Research Facilities & Equipment Center grant (2019R1A6C1010020).

Funding Information:
We thank N.S. Kim (Chonnam University), W.S. Ryu (Yonsei University), and J.Y. Lee (Catholic University) for sharing cell lines and plasmids. This work was supported by grants from the National Research Foundation of Korea (2021R1A2C3003675 and 2019R1A5A6099645 to S.Y.L.; 2020R1I1A1A01054670 to R.K.) and by a Korea Basic Science Institute National Research Facilities & Equipment Center grant (2019R1A6C1010020).

Publisher Copyright:
© 2022, The Author(s).

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