Send to

Choose Destination
Nat Immunol. 2015 Jul;16(7):689-97. doi: 10.1038/ni.3206.

The diverse role of RIP kinases in necroptosis and inflammation.

Author information

1] The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia. [2] Department of Medical Biology, University of Melbourne, Parkville, Australia.
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.


Inflammation is a healthy response to infection or danger and should be rapid, specific and terminated once the threat has passed. Inflammatory diseases, where this regulation fails, cause considerable human suffering. Treatments have successfully targeted pro-inflammatory cytokines, such as tumor-necrosis factor (TNF), that directly induce genes encoding inflammatory products. Inflammatory signals, including TNF, may also directly induce caspase-independent cell death (necroptosis), which can also elicit inflammation. Necroptosis was originally defined as being dependent on the kinase RIPK1 but is now known to be dependent on RIPK3 and the pseudo-kinase MLKL. Therefore, RIPK1, RIPK3 and MLKL are potential therapeutic targets. RIPK1 and RIPK3 also directly regulate inflammatory signaling, which complicates interpretation of their function but might alter their therapeutic utility. This Review examines the role of cell death, particularly necroptosis, in inflammation, in the context of recent insights into the roles of the key necroptosis effector molecules RIPK1, RIPK3 and MLKL.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center