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

J Exp Med. 2009 Apr 13;206(4):761-78. doi: 10.1084/jem.20082502. Epub 2009 Mar 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / immunology
  • Homeostasis
  • Lymphocytes / immunology
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Knockout
  • P-Selectin / genetics*
  • Proprotein Convertases
  • RNA / genetics
  • Receptors, Interleukin-7 / deficiency
  • Receptors, Interleukin-7 / genetics
  • Serine Endopeptidases / blood
  • Serine Endopeptidases / immunology*
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology*
  • Transcription, Genetic


  • Membrane Glycoproteins
  • P-Selectin
  • P-selectin ligand protein
  • Receptors, Interleukin-7
  • interleukin-7 receptor, alpha chain
  • RNA
  • Proprotein Convertases
  • Serine Endopeptidases
  • membrane-bound transcription factor peptidase, site 1