Thymic progenitor homing and lymphocyte homeostasis are linked via S1P-controlled expression of thymic P-selectin/CCL25

被引:82
作者
Gossens, Klaus [1 ]
Naus, Silvia [1 ]
Corbel, Stephane Y. [1 ]
Lin, Shujun [1 ]
Rossi, Fabio M. V. [1 ,2 ]
Kast, Joergen [1 ,3 ]
Ziltener, Hermann J. [1 ,4 ]
机构
[1] Univ British Columbia, Biomed Res Ctr, Vancouver, BC V6T 1Z3, Canada
[2] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada
[3] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z3, Canada
[4] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 1Z3, Canada
基金
加拿大健康研究院;
关键词
NECROSIS-FACTOR-ALPHA; SPHINGOSINE; 1-PHOSPHATE; P-SELECTIN; KAPPA-B; EPITHELIAL-CELLS; T-CELLS; BLOOD; PROLIFERATION; PRECURSORS; RECEPTOR;
D O I
10.1084/jem.20082502
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Thymic T cell progenitor (TCP) importation is a periodic, gated event that is dependent on the expression of functional P-selectin ligands on TCPs. Occupancy of intrathymic TCP niches is believed to negatively regulate TCP importation, but the nature of this feedback mechanism is not yet resolved. We show that P-selectin and CCL25 are periodically expressed in the thymus and are essential parts of the thymic gate-keeping mechanism. Periodicity of thymic TCP receptivity and the size of the earliest intrathymic TCP pool were dependent on the presence of functional P-selectin ligand on TCPs. Furthermore, we show that the numbers of peripheral blood lymphocytes directly affected thymic P-selectin expression and TCP receptivity. We identified sphingosine-1-phosphate (S1P) as one feedback signal that could mediate influence of the peripheral lymphocyte pool on thymic TCP receptivity. Our findings suggest a model whereby thymic TCP importation is controlled by both early thymic niche occupancy and the peripheral lymphocyte pool via S1P.
引用
收藏
页码:761 / 778
页数:18
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