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Recruitment of adult thymic progenitors is regulated by P-selectin and its ligand PSGL-1

Nature Immunology volume 6, pages 626–634 (2005)Cite this article

Abstract

The molecular mechanisms that direct the migration of early T lymphocyte progenitors to the thymus are unknown. We show here that P-selectin is expressed by thymic endothelium and that lymphoid progenitors in bone marrow and thymus bind P-selectin. Parabiosis, competitive thymus reconstitution and short-term homing assays indicated that P-selectin and its ligand PSGL-1 are functionally important components of the thymic homing process. Accordingly, thymi of mice lacking PSGL-1 contained fewer early thymic progenitors and had increased empty niches for prothymocytes compared with wild-type mice. Furthermore, the number of resident thymic progenitors controls thymic expression of P-selectin, suggesting that regulation of P-selectin expression by a thymic 'niche occupancy sensor' may be used to direct progenitor access.

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Figure 1: Bone marrow KLS cells (bmKLS), common lymphoid precursors (CLP; Lin−, c-Kitlo, Sca-1lo, IL-7R+), early thymic progenitors (ETP; c-Kit+, CD3−, CD4−, CD8−, CD44+, CD25−, Lin−) and circulating KLS cells (cKLS; putative circulating T precursors) bind P-selectin–human IgG chimeric protein.
Figure 2: P-selectin is expressed on the thymic vasculature.
Figure 3: Parabiotic mice reveal a role for C2, PSGL-1 and P-selectin in ETP homing to the thymus.
Figure 4: The competitive advantage of wild-type cells over C2-deficient and PSGL-1–deficient cells in thymic repopulation is dependent on environmental P-selectin.
Figure 5: Short-term thymic homing is dependent on C2, PSGL-1 and P-selectin.
Figure 6: Reduced number of early thymic progenitors and increased progenitor niche availability in PSGL-1–deficient thymi.
Figure 7: Thymic niche occupancy modulates P-selectin mRNA expression.

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Acknowledgements

We thank J. Marth for the C2-deficient mice; R. Stokes for helpful discussions; K.M. McNagny, G. Aversa and P. Orchansky for critical evaluation of the manuscript; and A. Johnson for assistance with flow cytometry. J.S.M. is supported by a CIHR Transplantation Fellowship. F.M.V.R. is supported by the Canada Research Chairs Program and the Michael Smith Foundation for Health Research. This work was supported by Canadian Institute for Health Research grants to H.J.Z. and to F.M.V.R. and by Networks of Centres of Excellence–StemNet funding to F.M.V.R.

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Author notes

  1. Stephane Y Corbel and Jasmeen S Merzaban: These authors contributed equally to this work.

Authors and Affiliations

  1. The Biomedical Research Centre, University of British Columbia, Vancouver, V6T 1Z3, British Columbia, Canada

    Fabio M V Rossi, Stephane Y Corbel, Jasmeen S Merzaban, Douglas A Carlow, Klaus Gossens, Jeffrey Duenas, Leslie So, Lin Yi & Hermann J Ziltener

  2. Department of Medical Genetics, University of British Columbia, Vancouver, V6T 1Z3, British Columbia, Canada

    Fabio M V Rossi

  3. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, V6T 1Z3, British Columbia, Canada

    Hermann J Ziltener

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Supplementary information

Supplementary Fig. 1

Gating used for the identification of the different subpopulations analyzed in Figure 1. (PDF 897 kb)

Supplementary Fig. 2

PSGL-1-deficient cells are evenly distributed in wild-type thymi. (PDF 4440 kb)

Supplementary Fig. 3

Engraftment of wild-type and PSGL-1-deficient cells in IL-7R-deficient mice. (PDF 464 kb)

Supplementary Fig. 4

PSGL-1-deficient cells engraft with high efficiency in the thymus after intrathymic injection. (PDF 474 kb)

Supplementary Table 1

Summary of thymic chimerisms in parabiotic mice. (PDF 30 kb)

Supplementary Table 2

Competitive repopulation by intrathymic injection. (PDF 30 kb)

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Rossi, F., Corbel, S., Merzaban, J. et al. Recruitment of adult thymic progenitors is regulated by P-selectin and its ligand PSGL-1. Nat Immunol 6, 626–634 (2005). https://doi.org/10.1038/ni1203

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