| First Author | Ventura S | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 11 | Pages | 2737-2747 |
| PubMed ID | 30337469 | Mgi Jnum | J:269102 |
| Mgi Id | MGI:6272950 | Doi | 10.1084/jem.20170852 |
| Citation | Ventura S, et al. (2018) A20-binding inhibitor of NF-kappaB (ABIN) 2 negatively regulates allergic airway inflammation. J Exp Med 215(11):2737-2747 |
| abstractText | 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 Map3k8(D270A/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. Tnip2(E256K) 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. |
