NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-κB-Dependent and -Independent Functions

• DOI: 10.1016/j.immuni.2016.02.020
• Publication Date: 2016-03-15T12:47:44Z
• Authors: Katerina Vlantis; Andy Wullaert; Apostolos Polykratis; Vangelis Kondylis; Marius Dannappel; Robin Schwarzer; Patrick Welz; Teresa Corona; Henning Walczak; Falk Weih; Ulf Klein; Michelle Kelliher; Manolis Pasparakis
• Keywords: RIPK1; Paneth cell; Intestinal epithelium; IκB kinase; RELB; FADD

Intestinal epithelial cells (IECs) regulate gut immune homeostasis, and impaired responses are implicated in the pathogenesis of inflammatory bowel diseases (IBD). IEC-specific ablation nuclear factor κB (NF-κB) essential modulator (NEMO) caused Paneth cell apoptosis antimicrobial expression ileum, as well colonocyte microbiota-driven chronic inflammation colon. Combined RelA, c-Rel, RelB deficiency IECs but not colitis, suggesting that NEMO prevents colon by NF-κB-independent functions. Inhibition receptor-interacting protein kinase 1 (RIPK1) activity or combined Fas-associated via death domain (FADD) RIPK3 prevented death, loss, colitis development mice with deficiency. Therefore, intestinal inhibiting RIPK1 activity-mediated IEC inhibitors could be effective treatment patients mutations possibly IBD.