creators_name: Sen, Pradip
creators_name: Wallet, Mark A
creators_name: Yi, Zuoan
creators_name: Huang, Yingsu
creators_name: Henderson, Michael
creators_name: Mathews, Clayton E
creators_name: Earp, H Shelton
creators_name: Matsushima, Glenn
creators_name: Baldwin, Albert S
creators_name: Tisch, Roland M
type: article
datestamp: 2012-02-17 16:38:14
lastmod: 2012-02-17 16:38:14
metadata_visibility: show
title: Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells.
ispublished: pub
subjects: R1
full_text_status: restricted
note: Copyright of this article belongs to American Society of Hematology.
abstract: Dendritic cells (DCs) play a key role in immune homeostasis and maintenance of self-tolerance. Tolerogenic DCs can be established by an encounter with apoptotic cells (ACs) and subsequent inhibition of maturation and effector functions. The receptor(s) and signaling pathway(s) involved in AC-induced inhibition of DCs have yet to be defined. We demonstrate that pretreatment with apoptotic but not necrotic cells inhibits activation of IkappaB kinase (IKK) and downstream NF-kappaB. Notably, receptor tyrosine kinase Mer (MerTK) binding of ACs is required for mediating this effect. Monocyte-derived DCs lacking MerTK expression (MerTKKD) or treated with blocking MerTK-specific antibodies (Abs) are resistant to AC-induced inhibition and continue to activate NF-kappaB and secrete proinflammatory cytokines. Blocking MerTK activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway prevents AC-induced inhibition. These results demonstrate an essential role for MerTK-mediated regulation of the PI3K/AKT and NF-kappaB pathways in AC-induced inhibition of monocyte-derived DCs.
date: 2007-01-15
date_type: published
publication: Blood
volume: 109
number: 2
publisher: American Society of Hematology
pagerange: 653-60
refereed: TRUE
issn: 0006-4971
official_url: http://bloodjournal.hematologylibrary.org/content/109/2/653.full.pdf+html
related_url_url: http://bloodjournal.hematologylibrary.org/content/109/2/653.full.pdf+html
related_url_type: pub
citation:   Sen, Pradip and Wallet, Mark A and Yi, Zuoan and Huang, Yingsu and Henderson, Michael and Mathews, Clayton E and Earp, H Shelton and Matsushima, Glenn and Baldwin, Albert S and Tisch, Roland M  (2007) Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells.  Blood, 109 (2).  pp. 653-60.  ISSN 0006-4971     
document_url: http://crdd.osdd.net/open/1058/1/sen2007.pdf