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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2531-2539.
Prepublished online as a Blood First Edition Paper on June 29, 2006; DOI 10.1182/blood-2006-05-024190.
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CHEMOKINES, CYTOKINES, AND INTERLEUKINS
Coordination between CCR7- and CCR9-mediated chemokine signals in prevascular fetal thymus colonization
Cunlan Liu,
Fumi Saito,
Zhijie Liu,
Yu Lei,
Shoji Uehara,
Paul Love,
Martin Lipp,
Shunzo Kondo,
Nancy Manley, and
Yousuke Takahama
From the Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Japan; the Department of Genetics, University of Georgia, Athens; the Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; the Department of Molecular Tumorgenetics and Immunogenetics, Max-Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany; and JEOL, Akishima, Tokyo, Japan.
Thymus seeding by T-lymphoid progenitor cells is a prerequisite for T-cell development. However, molecules guiding thymus colonization and their roles before and after thymus vascularization are unclear. Here we show that mice doubly deficient for chemokine receptors CCR7 and CCR9 were defective specifically in fetal thymus colonization before, but not after, thymus vascularization. The defective prevascular fetal thymus colonization was followed by selective loss of the first wave of T-cell development generating epidermal V 3+  T cells. Unexpectedly, CCL21, a CCR7 ligand, was expressed not by Foxn1-dependent thymic primordium but by Gcm2-dependent parathyroid primordium, whereas CCL25, a CCR9 ligand, was predominantly expressed by Foxn1-dependent thymic primordium, revealing the role of the adjacent parathyroid in guiding fetal thymus colonization. These results indicate coordination between Gcm2-dependent parathyroid and Foxn1-dependent thymic primordia in establishing CCL21/CCR7- and CCL25/CCR9-mediated chemokine guidance essential for prevascular fetal thymus colonization.

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