Format

Send to

Choose Destination
J Immunol. 2019 Aug 15;203(4):783-788. doi: 10.4049/jimmunol.1900202. Epub 2019 Jun 26.

Cutting Edge: TAK1 Safeguards Macrophages against Proinflammatory Cell Death.

Author information

1
Department of Molecular and Cellular Immunology, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621, Japan; hsanjo@shinshu-u.ac.jp.
2
Department of Molecular Pathology, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621, Japan.
3
Division of Animal Research, Research Center for Supports to Advanced Science, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
4
Institute of Immunology, University Clinics Ulm, D-89081 Ulm, Germany; and.
5
Laboratory of Host Defense, Immunology Frontier Research Center and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Osaka, Japan.
6
Department of Molecular and Cellular Immunology, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621, Japan.

Abstract

TGF-β-activated kinase 1 (TAK1) is known to play vital roles for innate and adaptive immunity; however, little is known about its potential role in limiting biological responses such as inflammation. In this study, we report that macrophage TAK1 participates in negatively regulating inflammation by restraining proinflammatory cell death. Macrophages from TAK1-deficient mice underwent cell death in response to LPS and poly(I:C), which took place in a manner dependent on TLR/TRIF-induced active Caspase8-mediated cleavage of gasdermin D, known as an executioner of pyroptosis. Likewise, TNF-α induced Caspase8-dependent gasdermin D processing following cell death in TAK1-deficient macrophages. Importantly, we demonstrated that this type of proinflammatory macrophage death is linked to susceptibility to septic shock in mice lacking TAK1 in macrophages in a TNF-α-independent fashion. Taken together, our data revealed that TAK1 acts as a signaling checkpoint to protect macrophages from unique proinflammatory cell death, ensuring the maintenance of innate immune homeostasis.

PMID:
31243089
DOI:
10.4049/jimmunol.1900202

LinkOut - more resources

Full Text Sources

Molecular Biology Databases

Miscellaneous

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center