IL-33 promotes DC development in BM culture by triggering GM-CSF production

• Published in: European journal of immunology Vol. 39; no. 12; pp. 3331 - 3342
• Main Authors: Mayuzumi, Nobuyasu, Matsushima, Hironori, Takashima, Akira
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 01.12.2009; WILEY‐VCH Verlag
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; CD11c Antigen - metabolism; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; Cytokines - pharmacology; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - metabolism; development GM‐CSF; Dose-Response Relationship, Drug; Female; Flow Cytometry; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; IL‐33; Interleukin-33; Interleukins - pharmacology; Mice; Mice, Inbred C57BL; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Time Factors
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200939472

Short-term DC cultures generated with GM-CSF and other cytokines have markedly improved our ability to study the immunobiology of DC. Here, we tested 65 cytokines individually for their potential to promote the generation of CD11c⁺ cells in a murine BM culture system. In addition to several cytokines known to promote DC survival and/or growth, IL-33 was found to augment DC development time- and dose-dependently. Although the resulting CD11c⁺ cells generated in the presence of IL-33 exhibited a typical dendritic morphology, they expressed MHC class II molecules only at modest levels, showed negligible responses to TLR ligands, produced no detectable IL-12 p70, displayed PD-L1 and PD-L2 on the surface, and failed to activate immunologically naïve T cells efficiently. IL-33-induced expansion of CD11c⁺ cells was completely blocked by anti-GM-CSF mAb, and GM-CSF mRNA and protein expression in BM culture was markedly elevated by added IL-33, indicating that IL-33 promotes in vitro DC generation indirectly by a GM-CSF-dependent manner. With regard to the cellular source, IL-33-dependent GM-CSF production was observed exclusively within the CD45⁺/FcεRI⁺ BM population. Not only do our results reinforce the notion that GM-CSF serves as a primary DC growth factor, but they also reveal a previously unrecognized mechanism supporting DC development.