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Krueger, A.* ; Willenzon, S.* ; Lyszkiewicz, M.* ; Kremmer, E. ; Forster, R.*

CC chemokine receptor 7 and 9 double-deficient hematopoietic progenitors are severely impaired in seeding the adult thymus.

Blood 115, 1906-1912 (2010)

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Open Access Green as soon as Postprint is submitted to ZB.

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T-cell development depends on recruitment of bone marrow-derived precursor cells to the thymus via a multistep adhesion cascade involving the chemokine receptor CCR9. However, CCR9 deficiency does not result in complete abrogation of progenitor entry into the adult thymus. Therefore, we tested the hypothesis that additional chemokine/chemokine receptor systems might play a role in this process. To this end, we generated mice deficient in both CCR9 and CCR7. Deficiency in both chemokine receptors resulted in severely reduced numbers of early T-cell progenitors and in near-complete abrogation of thymus reconstitution. Progenitors in bone marrow and peripheral blood remained largely unaffected in CCR7(-/-)CCR9(-/-) mice, and direct intrathymic transfer of precursors from CCR7(-/-)CCR9(-/-) mice as well as single-mutant mice showed that intrathymic differentiation of these precursors remained functional. Thus, our data reveal a previously unrecognized role of CCR7 in progenitor seeding of the adult thymus, which is largely masked by compensatory effects of CCR9 signals. In turn, CCR7 signals can partially compensate for CCR9 signals, thus explaining the rather mild phenotype of CCR9(-/-) mice with respect to progenitor seeding.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords T-cell development; Secondary lymphoid organs; Bone-marrow; Thymocytes; Microenvironments; Heterogeneity; Thymopoiesis; Lymphocytes; Migration; Precursor

ISSN (print) / ISBN 0006-4971

e-ISSN 1528-0020

Journal Blood

Quellenangaben Volume: 115, Issue: 10, Pages: 1906-1912

Publisher American Society of Hematology

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Molecular Immunology (IMI)