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

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

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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.

Item Type:	Article
Additional Information:	Copyright of this article belongs to American Society of Hematology.
Subjects:	R Medicine > R Medicine (General)
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	17 Feb 2012 16:38
Last Modified:	17 Feb 2012 16:38
URI:	http://crdd.osdd.net/open/id/eprint/1058

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