Thymic progenitor homing and lymphocyte homeostasis are linked via S1P-controlled expression of thymic P-selectin/CCL25.
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.
Gossens
Klaus
K
The Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Naus
Silvia
S
Corbel
Stephane Y
SY
Lin
Shujun
S
Rossi
Fabio M V
FM
Kast
Jürgen
J
Ziltener
Hermann J
HJ
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D006706:Homeostasis; D008214:Lymphocytes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D019007:P-Selectin / Q000235:genetics*; D043484:Proprotein Convertases; D012313:RNA / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000172:deficiency / Q000235:genetics; D012697:Serine Endopeptidases / Q000097:blood / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D014158:Transcription, Genetic
D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain; D012313:RNA; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C115575:membrane-bound transcription factor peptidase, site 1