Recently, researchers from the St. Jude Hospital discovered the dual effect of an enzyme called TAK1 in the innate immune response. It regulates inflammation and cell death.
Recently, researchers from the St. Jude Hospital discovered the dual effect of an enzyme called TAK1 in the innate immune response. It regulates inflammation and cell death.
TAK1 is known to promote inflammatory responses, and the authors found that the enzyme also inhibits inflammatory responses. The results were published in Journal of Experimental Medicine.
By studying macrophages in mice, the authors demonstrated that TAK1 can limit inflammatory responses and cell death by blocking the activation of NLRP3 inflammasomes. The NLRP3 inflammasome is a type of protein complex that, when activated, recognizes and resists viruses, bacteria, and other threats from the outside world. However, the activation of overactive NLRP3 is accompanied by the occurrence of diseases, including immune disorders.
"Although many studies have demonstrated the role of NLRP3 inflammasomes in the regulation of inflammation, infection, and immune responses, the activation and mechanism of action of NLRP3 have not been clearly revealed," said the author of the article, Kanneganti: "This new discovery shows that TAK1 is the key to regulate the homeostasis of NLRP3."
Activation of NLRP3 requires two signals, one of which is the role of TAK1. In the absence of TAK1, macrophages die without NLRP3 activation. However, there is no such effect in the presence of TAK1. However, wild-type macrophages also died after being treated with a TAK1 inhibitor.
The effects of defects in TAK1 include activation of RIPK1 and activation of caspase1. Activation of caspase1 produces both IL-18 and IL-1b cytokines that promote inflammatory cell death (cell death). The researchers also discovered a key factor that mediates this process in the absence of TAK1, including TNFa.
NLRP3 is one of the five major inflammatory bodies involved in innate immune regulation. However, the authors found that NLRP1 was the only inflammatory body that was activated in the absence of TAK1.
This study also showed the role of TAK1 inhibitors for cancer immunotherapy. By inhibiting the activity of TAK1, cell division can be blocked.
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