Published online before print September 16, 2008

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(Journal of Leukocyte Biology. 2008;84:1549-1556.)
© 2008 by Society for Leukocyte Biology

MIP-3 and MIP-1 rapidly mobilize dendritic cell precursors into the peripheral blood

Shan He^*, Qi Cao^*, Hiroyuki Yoneyama, Hailiang Ge^*, Yi Zhang and Yanyun Zhang^*,1

^* Institute of Health Sciences and Shanghai Institute of Immunology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Institutes of Medical Sciences, Shanghai, China;
Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, Tokyo, Japan; and
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA

¹ Correspondence: Institute of Health Sciences and Shanghai Institute of Immunology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Institutes of Medical Sciences, 225 South Chongqing Road, Shanghai 200025, China. E-mail: yyzhang{at}sibs.ac.cn

Acquisition of dendritic cells (DCs) or DC precursors in vitro is critical for DC-based immunotherapy. We reported previously that administration of MIP-1 mobilized a population of F4/80^–B220^–CD11c⁺ DC precursors into peripheral blood by the expression of CCR1 and CCR5. In this study, we identified a new subset of CCR6⁺CCR1^–CCR5^–B220^–CD11c⁺ cells in MIP-1-administered mice. When cultured with GM-CSF, IL-4, and TNF-, these cells differentiated into mature DCs, possessing the typical morphologic characteristics, phenotypes, and antigen-presenting function (termed CCR6⁺ DC precursors). Although it did not directly drive the CCR6⁺ DC precursors, MIP-1 could recruit a population of F4/80⁺CD11c^– monocyte/macrophage-producing MIP-3 in the peripheral blood to mobilize a CCR6⁺ DC precursor subset of B220^–CD11c⁺ DC precursors. Importantly, exogenous administration of MIP-3 significantly enhanced MIP-1-induced mobilization of DC precursors. Moreover, these MIP-3- and MIP-1-mobilized DC precursors could be prepared for a DC vaccine capable of eliciting CTL responses to tumor cells, leading to tumor rejection in vitro and in vivo. Taken together, this study further demonstrates the mechanism of DC precursor mobilization induced by MIP-1; that is, besides mobilizing DC precursors with CCR1 and CCR5 expressions, MIP-1 recruited F4/80⁺CD11c^– monocyte/macrophage-producing MIP-3, which finally mobilized the CCR6⁺ DC precursor subset to amplify the B220^–CD11c⁺ DC precursor population. Furthermore, combined administration of MIP-3 and MIP-1 may be an efficient strategy for collecting a large number of DCs appropriate for immunotherapy.

Key Words: chemokine • recruited DC • DC-based vaccine