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Coordination between CCR7- and CCR9-mediated chemokine signals in pre-vascular fetal thymus colonization

Official URL:https://doi.org/10.1182/blood-2006-05-024190
PubMed:View item in PubMed
Creators Name:Liu, C. and Saito, F. and Liu, Z. and Lei, Y. and Uehara, S. and Love, P. and Lipp, M. and Kondo, S. and Manley, N. and Takahama, Y.
Journal Title:Blood
Journal Abbreviation:Blood
Volume:108
Number:8
Page Range:2531-2539
Date:15 October 2006
Keywords:CC Chemokines, CCR Receptors, CCR7 Receptors, Chemokine CCL21, Chemokine Receptors, Forkhead Transcription Factors, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Nude Mice, Physiologic Neovascularization, Pregnancy, Signal Transduction, Thymus Gland, Animals, Mice
Abstract: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 pre-vascular fetal thymus colonization was followed by selective loss of the first wave of T-cell development generating epidermal V gamma 3(+) gamma delta 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 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 pre-vascular fetal thymus colonization.
ISSN:0006-4971
Publisher:American Society of Hematology (U.S.A.)
Item Type:Article

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