A20-binding inhibitor of NF-κB (ABIN) 2 negatively regulates allergic airway inflammation
More about Open Access at the CrickAuthors list
Sonia Ventura Florencia Cano Yashaswini Kannan Felix Breyer Michael J Pattison Mark S Wilson Steve LeyAbstract
TPL-2 MAP 3-kinase promotes inflammation in numerous mouse disease models and is an attractive anti-inflammatory drug target. However, TPL-2–deficient (Map3k8−/−) mice develop exacerbated allergic airway inflammation to house dust mite (HDM) compared with wild type controls. Here, we show that Map3k8D270A/D270A mice expressing kinase dead TPL-2 had an unaltered response to HDM, indicating that the severe airway inflammation observed in Map3k8−/− mice is not due to blockade of TPL-2 signaling and rather reflects a TPL-2 adaptor function. Severe allergic inflammation in TPL-2–deficient mice was likely due to reduced levels of ABIN-2 (TNIP2), whose stability depends on TPL-2 expression. Tnip2E256K knock-in mutation, which reduced ABIN-2 binding to A20, augmented the HDM-induced airway inflammation, but did not affect TPL-2 expression or signaling. These results identify ABIN-2 as a novel negative regulator of allergic airway responses and importantly indicate that TPL-2 inhibitors would not have unwanted allergic comorbidities.
Journal details
Journal Journal of Experimental Medicine
Volume 215
Issue number 11
Pages 2737-2747
Available online
Publication date
Full text links
Publisher website (DOI) 10.1084/jem.20170852
Figshare View on figshare
Europe PubMed Central 30337469
Pubmed 30337469
Keywords
Related topics
Type of publication