Thymocytes in Lyve1-CRE/S1pr1f/f mice accumulate in the thymus due to cell-intrinsic loss of sphingosine-1-phosphate receptor expression

Frontiers in Immunology

Szandor Simmons¹  Masayuki Miyasaka¹  Naoko Sasaki¹  Akira Takeda²  Marko Salmi²  Pia Rantakari²  Mohammad Shahadat Hossain²  Sirpa Jalkanen² 

[1] Osaka University;University of Turku;

关键词: Egress;    Sphingosine-1-phosphate;    Thymus;    S1PR1;    LYVE1;   

DOI  :  10.3389/fimmu.2016.00489

来源: DOAJ

【 摘 要 】

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/S1pr1f/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/S1pr1f/f mice exhibited an egress-competent phenotype (HSAlow, CD62Lhigh, and Qa-2high), but were CD69high and lacked S1PR1 expression. In addition, CD4 SP thymocytes from these mice were unable to migrate to the periphery after their intra-thymic injection into wild-type (WT) mice. In contrast, WT T cells could migrate to the periphery in both WT and Lyve1-CRE/S1pr1f/f thymuses. These results demonstrated that thymocyte egress is mediated by T cell-, but not stromal cell-expressed S1PR1 and caution against using the Lyve1-CRE system for selectively gene deletion in lymphatic endothelial cells.

【 授权许可】

Unknown