期刊
BLOOD
卷 109, 期 2, 页码 653-660出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-04-017368
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- NIAID NIH HHS [R01 AI050736, AI35098, AI066075, AI50736, R01 AI035098, U19 AI056374, R01 AI066075, AI056374, R37 AI035098] Funding Source: Medline
- NIDCR NIH HHS [P60 DE013079, 1-P60-DE 13079] Funding Source: Medline
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 I kappa B kinase (IKK) and downstream NF-kappa B. Notably, receptor tyrosine kinase Mer (MerTK) binding of ACs is required for mediating this effect. Monocyte-derived DCs lacking MerTK expression (MerTK(KD)) or treated with blocking MerTK-specific antibodies (Abs) are resistant to AC-induced inhibition and continue to activate NF-kappa B 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-kappa B pathways in AC-induced inhibition of monocytederived DCs.
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