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Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells.
 
Creator Sen, Pradip
Wallet, Mark A
Yi, Zuoan
Huang, Yingsu
Henderson, Michael
Mathews, Clayton E
Earp, H Shelton
Matsushima, Glenn
Baldwin, Albert S
Tisch, Roland M
 
Subject R Medicine (General)
 
Description 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.
 
Publisher American Society of Hematology
 
Date 2007-01-15
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/1058/1/sen2007.pdf
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
 
Relation http://bloodjournal.hematologylibrary.org/content/109/2/653.full.pdf+html
http://crdd.osdd.net/open/1058/