A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Thymocytes in Lyve1-CRE/S1pr1(f/f) Mice accumulate in the Thymus due to cell-intrinsic loss of sphingosine-1-Phosphate receptor expression
Tekijät: Takeda A, Hossain MS, Rantakari P, Simmons S, Sasaki N, Salmi M, Jalkanen S, Miyasaka M
Kustantaja: FRONTIERS MEDIA SA
Julkaisuvuosi: 2016
Journal: Frontiers in Immunology
Tietokannassa oleva lehden nimi: FRONTIERS IN IMMUNOLOGY
Lehden akronyymi: FRONT IMMUNOL
Artikkelin numero: UNSP 489
Vuosikerta: 7
Sivujen määrä: 11
ISSN: 1664-3224
DOI: https://doi.org/10.3389/fimmu.2016.00489
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 (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/S1pr1f/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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