Document Detail

miR-146a mediates protective innate immune tolerance in the neonate intestine.
MedLine Citation:
PMID:  20951969     Owner:  NLM     Status:  In-Process    
After birth, the intestinal mucosa undergoes a dramatic transition from a sterile protected site to an environmentally exposed and permanently colonized surface. The mechanisms that facilitate this transition are ill defined. Here, we demonstrate that microRNA-146a-mediated translational repression and proteolytic degradation of the essential Toll-like receptor (TLR) signaling molecule interleukin 1 receptor associated kinase 1 (IRAK1) is sufficient to induce intestinal epithelial innate immune tolerance and provide protection from bacteria-induced epithelial damage in neonates. Despite low IRAK1 protein levels, continuous TLR4- and IRAK1-dependent signal transduction induced by intraepithelial endotoxin persistence during the neonatal period maintains tolerance through sustained miR-146a expression. Strikingly, it additionally facilitates transcription of a distinct set of genes involved in cell survival, differentiation, and homeostasis. Thus, our results identify the underlying molecular mechanisms of intestinal epithelial innate immune tolerance during the neonatal period and characterize tolerance as an active condition involved in the establishment of intestinal mucosal homeostasis.
Cécilia Chassin; Magdalena Kocur; Johanna Pott; Claudia U Duerr; Dominique Gütle; Michael Lotz; Mathias W Hornef
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell host & microbe     Volume:  8     ISSN:  1934-6069     ISO Abbreviation:  Cell Host Microbe     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101302316     Medline TA:  Cell Host Microbe     Country:  United States    
Other Details:
Languages:  eng     Pagination:  358-68     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, 30625 Hannover, Germany.
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Comment In:
Cell Host Microbe. 2010 Oct 21;8(4):303-4   [PMID:  20951963 ]
Nat Rev Immunol. 2010 Dec;10(12):810

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