Title: The tyrosine kinase MerTK negatively regulates the function of murine natural killer T cells (47.7)
Abstract:Abstract NKT cells have multiple effector functions including the capacity to prevent the growth of tumors, and the ability to immunoregulate autoimmunity. The key events that regulate NKT cell activa...Abstract NKT cells have multiple effector functions including the capacity to prevent the growth of tumors, and the ability to immunoregulate autoimmunity. The key events that regulate NKT cell activation and function remain ill-defined. Recently, NKT cells were shown to express the receptor tyrosine kinase (RTK) Mer (MerTK). MerTK belongs to the Tyro3 RTK family. These RTK mediate the clearance of apoptotic cells (AC) and regulate the activation of dendritic cells (DC) and macrophages. Recently, we demonstrated that DC lacking MerTK are resistant to the inhibitory effects of AC. In this study, we sought to determine the role for MerTK in regulating NKT cell activation and function. To address this issue C57BL/6 mice (B6) lacking MerTK expression (B6.mertkkd/kd) were employed. Our data demonstrates that unprimed B6.mertkkd/kd NKT cells exhibit a heightened level of activation in comparison to wild-type NKT cells, while long-term exposure to alpha-GalCer (αGC) activated both sets of NKT cells similarly. Previously primed B6.mertkkd/kd NKT cells secreted cytokines upon subsequent stimulation with αGC, whereas wild-type NKT cells failed to be activated and remained anergized. In addition, stimulation with αGC pulsed DC, IFNγ and IL-4 production was significantly increased in NKT cells prepared from B6.mertkkd/kd versus B6 mice. These results indicate that MerTK serves to down-regulate cytokine production by NKT cells.Read More
Publication Year: 2009
Publication Date: 2009-04-01
Language: en
Type: article
Indexed In: ['crossref']
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