Skip to Main Content
Article navigation

IRAK4 is a member of IL-1 receptor (IL-1R)–associated kinase (IRAK) family and has been shown to play an essential role in Toll-like receptor (TLR)–mediated signaling. We recently generated IRAK4 kinase-inactive knock-in mice to examine the role of kinase activity of IRAK4 in TLR-mediated signaling pathways. The IRAK4 kinase–inactive knock-in mice were completely resistant to lipopolysaccharide (LPS)- and CpG-induced shock, due to impaired TLR-mediated induction of proinflammatory cytokines and chemokines. Although inactivation of IRAK4 kinase activity did not affect the levels of TLR/IL-1R–mediated nuclear factor κB activation, a reduction of LPS-, R848-, and IL-1–mediated mRNA stability contributed to the reduced cytokine and chemokine production in bone marrow–derived macrophages from IRAK4 kinase–inactive knock-in mice. Both TLR7- and TLR9-mediated type I interferon production was abolished in plasmacytoid dendritic cells isolated from IRAK4 knock-in mice. In addition, influenza virus–induced production of interferons in plasmacytoid DCs was also dependent on IRAK4 kinase activity. Collectively, our results indicate that IRAK4 kinase activity plays a critical role in TLR-dependent immune responses.

You do not currently have access to this content.
Don't already have an account? Register

or Create an Account

Close Modal
Close Modal

Gift article access

As a benefit of your subscription, you can share temporary access to restricted articles.

Each link will stop working after 30 days or 10 uses. You may create up to 10 links in a 30 day period.

Please sign in to your personal account to gift article access.

Register

Gift article access

As a benefit of your subscription, you can share temporary access to restricted articles.

Each link will stop working after 30 days or 10 uses. You may create up to 10 links in a 30 day period.

Gift articles remaining: --

Gift article access

Each link will stop working after 30 days or 10 uses. You may create up to 10 links in a 30 day period.

Gift articles remaining: --

Gift article access

As a benefit of your subscription, you can share temporary access to restricted articles.

Each link will stop working after 30 days or 10 uses.

You have reached the limit of 10 links within a 30 day period.