APIP regulates the priming of canonical NLRP3 and non-canonical Caspase-11/4 inflammasomes by binding to TRAF6

Kwangmin Jung, Meiko Kawamura, Bitna Lim, Manabu Abe, Kenji Sakimura, Masaaki Komatsu and Yong-Keun Jung ()
Additional contact information
Kwangmin Jung: Seoul National University, School of Biological Sciences
Meiko Kawamura: Niigata University, Department of Animal Model Development, Brain Research Institute
Bitna Lim: Seoul National University, School of Biological Sciences
Manabu Abe: Niigata University, Department of Animal Model Development, Brain Research Institute
Kenji Sakimura: Niigata University, Department of Animal Model Development, Brain Research Institute
Masaaki Komatsu: Juntendo University Graduate School of Medicine, Department of Physiology
Yong-Keun Jung: Seoul National University, School of Biological Sciences

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Apaf-1-interacting protein (APIP) has been implicated in inflammation-related processes, including myocardial infarction and cancer progression. However, its role in systemic inflammation remains elusive. Here, we investigate the APIP-mediated regulation of inflammasome activity in mice and human macrophages. Loss of APIP in the myeloid lineage (Apip cKO mice) compromises the activation of canonical NLRP3 and non-canonical caspase-11 inflammasomes, reducing pyroptosis in bone marrow-derived macrophages (BMDM). Conversely, these inflammatory responses are enhanced in BMDMs from APIP-transgenic mice. Consistently, APIP knockdown in human macrophages inhibits the activation of NLRP3 and caspase-4 inflammasomes. Mechanistically, APIP binds to TRAF6, activating downstream NF-κB and JNK signaling and facilitating the priming of both inflammasomes. Importantly, systemic inflammation induced by LPS or bacterial infection is attenuated in Apip cKO mice but exacerbated in APIP-transgenic mice. Thus, our findings suggest that APIP is crucial in regulating both canonical and non-canonical inflammasomes, presenting a potential therapeutic target for inflammatory diseases.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-65893-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65893-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-65893-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().