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10.3389/fimmu.2016.00489

http://scihub22266oqcxt.onion/10.3389/fimmu.2016.00489
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suck abstract from ncbi


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pmid27877175
      Front+Immunol 2016 ; 7 (ä): 489
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  • Thymocytes in Lyve1-CRE/S1pr1(f/f) Mice Accumulate in the Thymus due to Cell-Intrinsic Loss of Sphingosine-1-Phosphate Receptor Expression #MMPMID27877175
  • Takeda A ; Hossain MS ; Rantakari P ; Simmons S ; Sasaki N ; Salmi M ; Jalkanen S ; Miyasaka M
  • Front Immunol 2016[]; 7 (ä): 489 PMID27877175 show ga
  • T cell emigration from the thymus is essential for immunological homeostasis. While stromal cell-produced sphingosine-1-phosphate (S1P) has been shown to promote thymocyte egress via the S1P receptor, S1PR1, the significance of S1P/S1PR1 signaling in the thymic stromal cells that surround T cells remains unclear. To address this issue, we developed conditional knockout mice (Lyve1-CRE/S1pr1(f/f) mice) in which S1pr1 was selectively targeted in cells expressing the lymphatic endothelial cell marker, Lyve1. In these mice, T cells were significantly reduced in secondary lymphoid tissues, and CD62L(+) mature CD4 and CD8 single-positive (SP) T cells accumulated in the medulla failed to undergo thymus egress. Using a Lyve1 reporter strain in which Lyve1 lineage cells expressed tdTomato fluorescent protein, we unexpectedly found that a considerable proportion of the thymocytes were fluorescently labeled, indicating that they belonged to the Lyve1 lineage. The CD4 and CD8 SP thymocytes in Lyve1-CRE/S1pr1(f/f) mice exhibited an egress-competent phenotype (HSA(low), CD62L(high), and Qa-2(high)), but were CD69(high) and lacked S1PR1 expression. In addition, CD4 SP thymocytes from these mice were unable to migrate to the periphery after their intrathymic injection into wild-type (WT) mice. In contrast, WT T cells could migrate to the periphery in both WT and Lyve1-CRE/S1pr1(f/f) thymuses. These results demonstrated that thymocyte egress is mediated by T cell-expressed, but not stromal cell-expressed, S1PR1 and caution against using the Lyve1-CRE system for selectively gene deletion in lymphatic endothelial cells.
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