Differential requirement for the SAP-Fyn interaction during NK T cell development and function.
Differential requirement for the SAP-Fyn interaction during NK T cell development and function.
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DOI：
10.4049/jimmunol.181.4.2311
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发表时间：
2008-08-15
期刊：
影响因子：
--
通讯作者：
Nichols KE
中科院分区：
文献类型：
--
作者：
Nunez-Cruz S;Yeo WC;Rothman J;Ojha P;Bassiri H;Juntilla M;Davidson D;Veillette A;Koretzky GA;Nichols KE
The adaptor molecule SAP plays a critical role during natural killer T (NKT) cell development in humans and mice. In CD4+ T cells, SAP interacts with the tyrosine kinase Fyn to deliver signals required for TCR-induced TH2-type cytokine production. To determine whether the SAP-dependent signals controlling NKT cell ontogeny rely on its binding to Fyn, we used the OP9-DL1 system to initiate structure function studies of SAP in murine NKT cell development. In cultures containing wild type (WT) hematopoietic progenitors, we noted the transient emergence of cells that reacted with the NKT cell-specific agonist α-galactosyl ceramide (α-GC) and its analogue PBS57. Sap−/− cells failed to give rise to NKT cells in vitro; however, their development could be rescued by re-expression of WT SAP. Emergence of NKT cells was also restored by a mutant version of SAP (SAP R78A) that cannot bind to Fyn, but with less efficiency than WT SAP. This finding was accentuated in vivo in SapR78A knock-in mice as well as SapR78A competitive bone marrow chimeras, which retained NKT cells but at significantly reduced numbers compared to controls. Unlike SapR78A CD4+ T cells, which produce reduced levels of IL-4 following TCR ligation, α-GC-stimulated NKT cells from the livers and spleens of SapR78A mice produced TH2 cytokines and activated NK cells in a manner mimicking WT cells. Thus, SAP appears to use differential signaling mechanisms in NKT cells, with optimal ontogeny requiring Fyn binding, while functional responses occur independent of this interaction.
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DOI：
10.1084/jem.20061442
发表时间：
2007-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Besseyrias V;Fiorini E;Strobl LJ;Zimber-Strobl U;Dumortier A;Koch U;Arcangeli ML;Ezine S;Macdonald HR;Radtke F
通讯作者：
Radtke F
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DOI：
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发表时间：
2005-03-07
期刊：
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影响因子：
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期刊：
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影响因子：
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