Koehn, Jadranka, Huesken, Dieter, Jaritz, Markus, Rot, Antal, Zurini, Mauro, Dwertmann, Anne, Beutler, Bruce and Korthauer, Ulf (2007) Assessing the function of human UNC-93B in Toll-like receptor signaling and major histocompatibility complex II response. Human Immunology, 68 (11). pp. 871-878. ISSN 0198-8859

Abstract

The high sequence identity observed between UNC-93B of mouse and human imply common evolutionary ancestors and a conserved function. A nonconservative point mutation in the mouse Unc93b1 gene has been associated with defective Toll-like receptor (TLR) signaling and impaired major histocompatibility complex (MHC) I and II restricted antigen responses. Like murine UNC-93B, the human homologue is predicted to form 12 transmembrane domains, and it localizes to the endoplasmic reticulum. In human beings its expression is highest in professional antigen-presenting cells such as dendritic cells and macrophages. Interestingly, UNC-93B itself is specifically induced by TLR3 signaling in monocyte-derived dendritic cells and macrophages. To study the effect of UNC-93B deficiency in TLR signaling and antigen-presentation in human beings, UNC-93B message was knocked down in monocyte-derived dendritic cells and a reduced TNFalpha production in response to TLR3 agonists was observed. In the same experiment, the achieved knockdown had no effect on an MHC II-dependent antigen response, suggesting that the reduced quantity of human UNC-93B was still capable of supporting class II antigen presentation or that UNC-93B is not required for class II antigen presentation in human antigen-presenting cells.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.humimm.2007.07.007
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	Dendritic cells; siRNA; Adaptive immune system; Innate immunity; Toll-like receptors
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.humimm.2007.07.007
Date Deposited:	14 Dec 2009 14:01
Last Modified:	14 Dec 2009 14:01
URI:	https://oak.novartis.com/id/eprint/339