Journal
CLINICAL IMMUNOLOGY
Volume 142, Issue 3, Pages 296-307Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2011.11.006
Keywords
Galectin-9; M-CSF; pDC-like M phi; NK cell; Anti-tumor immunity
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Funding
- Japan Society for Promotion of Science (JSPS) [20790570, 22590360, 23256004, 23591438]
- Ministry of Health, Labor and Welfare, Kagawa University
- Japanese Ministry of Education, Culture, Sports, Science, and Technology
- Grants-in-Aid for Scientific Research [23256004, 22590360, 23591438, 20790570] Funding Source: KAKEN
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Galectin-9 (Gal-9) expanded plasmacytoid dendritic cell-like macrophages (pDC-M phi s) in lung cancer-bearing mice and prolonged the survival. Gal-9 increased the frequency of CD11c(high) cells in M-CSF- but not GM-CSF-induced M phi s in vitro in a Tim-3 independent manner. CD11C(high) cells differentiated with M-CSF+Gal-9 expressed pDC-M phi markers, such as PDCA-1 and F4/80. These cells expressed high TLR7, TLR8 and TLR9, although they exhibited decreased IFN-alpha mRNA levels. LPS or LLC stimulation further elevated pDC-M phi markers, indicating that M-CSF+Gal-9-induced M phi s were pDC-M phi precursors. Moreover, LPS stimulation resulted in the increased IRF7 and E2-2 levels, suggesting that the pDC-M phi precursors matured into pDC-M phi s. These matured pDC-M phi s augmented NK cell-mediated cytotoxicity though they did not produce IFN-alpha upon TLR7 or TLR9 stimulation. The present results suggest that Gal-9 induces M phi s to differentiate to pDC-M phi s, and that this switch in differentiation favors the activation of NK cells that are able to prolong the survival of tumor-bearing mice. (C) 2011 Elsevier Inc. All rights reserved.
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