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Blood, Vol. 93 No. 10 (May 15), 1999:
pp. 3225-3232
Chemotactic Response Toward Chemokines and Its Regulation by
Transforming Growth Factor- 1 of Murine Bone Marrow Hematopoietic
Progenitor Cell-Derived Different Subset of Dendritic Cells
Masafumi Ogata,
Yi Zhang,
Yong Wang,
Meiji Itakura,
Yan-yun Zhang,
Akihisa Harada,
Shin-ichi Hashimoto, and
Kouji Matsushima
From the Department of Molecular Preventive Medicine and CREST,
School of Medicine, The University of Tokyo, Tokyo, Japan; and the
Department of Ophthalmology, Faculty of Medicine, Kanazawa University,
Kanazawa, Japan.
Dendritic cells (DCs) are highly specialized antigen-presenting
cells that distribute widely in all organs. DCs initiate the primary
immune response and activate naive T cells and B cells responsible for
the acquired immunity. In this study, CCR7 mRNA was proved to be
expressed in DCs and their precursors derived from murine bone
marrow-derived hematopoietic progenitor cells (HPCs), whereas CCR1 mRNA
was expressed in both CD11b /dullCD11c+ and
CD11b+hiCD11c+ DC precursors. CCR6 mRNA was
not detected in any murine DC populations. In agreement with the
chemokine receptor mRNA expression by each population in the DC
differentiation pathway, SLC (also termed as MIP-3 ), one of the
ligands for CCR7, strongly and selectively chemoattracted both
CD11b/dullCD11c+ and
CD11b+hiCD11c+ DC precursors (days 6 to 7)
and more mature DCs (days 13 to 14). We have recently found that
transforming growth factor-1 (TGF-1), a cytokine that is
essential for the appearance of Langerhans cells in the skin, polarizes
murine HPCs to generate Langerhans-like cells through
monocyte/macrophage differentiation pathway. We observed here that
TGF-1 not only inhibited the expression of CCR7 in DCs and DC
precursors derived from HPCs, but also inhibited the migration of these
cells in response to SLC. This is the first report describing the
chemokine and chemokine receptors responsible for murine DC migration
and downregulation of DC migration by TGF-1.
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