Three chemokine receptors cooperatively regulate homing of hematopoietic progenitors to the embryonic mouse thymus

Proc Natl Acad Sci U S A. 2011 May 3;108(18):7517-22. doi: 10.1073/pnas.1016428108. Epub 2011 Apr 18.

Abstract

The thymus lacks self-renewing hematopoietic cells, and thymopoiesis fails rapidly when the migration of progenitor cells to the thymus ceases. Hence, the process of thymus homing is an essential step for T-cell development and cellular immunity. Despite decades of research, the molecular details of thymus homing have not been elucidated fully. Here, we show that chemotaxis is the key mechanism regulating thymus homing in the mouse embryo. We determined the number of early thymic progenitors in the thymic rudiments of mice deficient for one, two, or three of the chemokine receptor genes, chemokine (C-C motif) receptor 9 (Ccr9), chemokine (C-C motif) receptor 7 (Ccr7), and chemokine (C-X-C motif) receptor 4 (Cxcr4). In the absence of all three chemokine receptors, thymus homing was reduced about 100-fold both before and after vascularization of the thymic rudiment. In the absence of only two of these three chemokine receptor genes, thymus homing was much less affected (only two- to 10-fold), indicating that the chemotactic regulation of thymus homing is remarkably robust. Our results reveal the redundant roles of Ccr9, Ccr7, and Cxcr4 for thymic homing and provide a framework to examine the regulation of progenitor homing in the postnatal thymus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemotaxis / physiology*
  • Flow Cytometry
  • Hematopoietic Stem Cells / physiology*
  • Immunohistochemistry
  • Mice
  • Mice, Mutant Strains
  • Receptors, Chemokine / metabolism*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • Thymus Gland / cytology*
  • Thymus Gland / embryology*
  • Thymus Gland / metabolism

Substances

  • Receptors, Chemokine